Ionic polymer compositions

ABSTRACT

The present disclosure pertains to ionic polymer compositions, including semi.- and fully interpenetrating polymer networks, methods of making, such ionic polymer compositions, articles made from such ionic polymer compositions, and methods of making such articles and packaging, for such articles.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.17/391,212, filed Aug. 2, 2021, which is a continuation of U.S.application Ser. No. 17,091,787, filed Nov. 6. 2020, now U.S. Pat. No.11,110,200, which is a continuation of U.S. application Ser. No.16/514,279, filed Jul. 17, 2019, now U.S. Pat. No. 10,869,950, which isa continuation-in-part of U.S. application Ser. No. 16/246,292, filedJan. 11, 2019, entitled “Ionic Polymer Compositions,” which claims thebenefit of U.S. application Ser. No. 62/699,497, filed Jul. 17, 2018 andentitled “Ionic Polymer Compositions”. The disclosure of each of thepreceding applications is hereby incorporated by reference in itsentirety.

FIELD OF THE DISCLOSURE

The present disclosure pertains to ionic polymer compositions, includingsemi- and fully interpenetrating polymer networks, methods of makingsuch ionic polymer compositions, articles made from such ionic polymercompositions, and methods of making such articles and packaging for sucharticles.

BACKGROUND OF THE DISCLOSURE

Fully interpenetrating polymer networks (IPN's) andsemi-interpenetrating polymer networks (“semi-IPN's”) have been createdfrom a variety of starting materials and have been used for a. varietyof applications. IPN's and semi-IPN's can combine the beneficialproperties of each of the polymers from which they are made.

IPN's and semi-IPN's are described for biomedical applications, forexample, in U.S. Patent Publ. No. 2009/0008846, U.S. Patent Publ. No.2013/0096691, U.S. Patent Publ. No. 2017/0107370, U.S. Patent Publ, No,2012/0045651, U.S. Patent Publ. No. 2012/0209396, U.S. Patent .Publ. No.2017/0327624, U.S. Patent Publ. No. 2013/0131741, and WO 201.7/027590.

SUMMARY OF THE DISCLOSURE

For purposes of this application, “carboxylic acid groups” may refer toboth non-ionized (protonated) and ionized (carboxylate) forms of thesegroups. For purposes of this application, “sulfonic acid groups” mayrefer to both non-ionized (protonated) and ionized (sulfonate) forms ofthese groups.

For purposes of this application, an “interpenetrating polymer network”or “IPN” is a material comprising two or more polymer networks which areat least partially interlaced on a molecular scale, but not covalentlybonded to each other. and cannot be separated unless chemical bonds arebroken. A “semi-interpenetrating polymer network” or “semi-IPN” is amaterial comprising one or more polymer networks and one or more linearor branched polymers characterized by the penetration on a molecularscale of at least one of the networks by at least some of the linear orbranched macromolecules. Semi-interpenetrating polymer networks aredistinguished from interpenetrating polymer networks because theconstituent linear or branched polymers can, in principle, be separatedfrom the constituent polymer network(s) without breaking chemical bonds;they are polymer blends.

A “polymer” is a substance comprising macromolecules, includinghomopolymers (a polymer derived from one species of monomer) andcopolymers (a polymer derived from more than one species of monomer). A“hydrophobic polymer” is a pre-formed polymer network having at leastone of the following two properties: (1) a surface water contact angleof at least 45° and (2) exhibits water absorption of 2.5% or less after24 hours at room temperature according to ASTM test standard D570. A“hydrophilic polymer” is a polymer network having a surface watercontact angle less than 45″ and exhibits water absorption of more than2.5% after 24 hours at room temperature according to ASTM test standardD570. An “ionic polymer” is defined as polymer comprised ofmacromolecules containing ionic monomers (e.g., monomers withcarboxylate group, sulfonate groups, or both), ionizable monomers (e.g.,monomers with protonated carboxyl groups, protonated sulfonate groups,or both , or both ionic monomers and ionizable monomers, typically, atleast 2% by weight ionic or ionizable monomers (or both), irrespectiveof their nature and location. A “thermoset polymer” is one that doesn'tmelt when heated, unlike a thermoplastic polymer. Thermoset polymers“set” into a given shape when first made and afterwards do not flow ormelt, but rather decompose upon heating and are often highly crosslinkedand/or covalently crosslinked. A “thermoplastic polymer” is one whichmelts or flows when heated, unlike thermoset polymers. Thermoplasticpolymers are usually not. covalently crosslinked. “Phase separation” isdefined as the conversion of a single-phase system into a multi-phasesystem; especially the separation of two immiscible blocks of a blockco-polymer into two phases, with the possibility of a small interphasein which a small degree of mixing occurs.

In certain aspects, the present disclosure pertains to ionic polymersthat comprise a combination of carboxylic acid groups and sulfonic acidgroups. In certain of these aspects, the present disclosure pertains toionic polymers that comprise a combination of underivatized groups andsulfonic-acid-derivatized groups.

in certain aspects, the present disclosure pertains to ionic polymersthat comprise a combination of underivatized carboxylic acid groups andsulfonic-acid-derivatized groups, includingamino-sulfonic-acid-derivatized carboxylic acid groups.

In certain aspects, sulfonic-acid-derivatized groups are only found atthe surface of the ionic polymer. In certain aspects,sulfonic-acid-derivatized groups may extend from a surface of the ionicpolymer and into a bulk of the ionic polymer by a distance of at least10 microns, at least 50 microns, at least 100 microns, at least 250microns, at least 500 microns, at least 1000 microns, least 2500microns, or at least 5000 microns, at least 10000 microns or more, forexample, extending into the bulk of the ionic polymer by a distanceranging from 0 microns to 10 microns to 25 microns to 50 microns to 100microns to 250 microns to 500 microns to 1000 microns to 2500 microns to5000 microns to 10000 microns or more,

In certain aspects, at least 1%, at least 5%, at least 10%, at least15%, at least 20%, at least 25%, at least 50%, at least 75%, at least80%, at least 85%, at least 90%, at least 95% or all of the thickness ofthe ionic polymer has sulfonic-acid derivatized groups.

In certain aspects, the sulfonic-acid-derivatized groups extend from asurface of the ionic polymer into a hulk of the ionic polymer and arepresent in detectable amounts up to a distance from the surface of atleast 250 microns, at least 500 microns, at least 1000 microns, at least2500 microns, at least 5000 microns, or at least 10000 microns, or more,for example, being present in detectable amounts at a distance from thesurface ranging from 250 microns to 500 microns to 1000 microns to 2500microns to 5000 microns to 10000 microns or more.

In certain of these aspects, a concentration ofsulfonic-acid-derivatized groups in the ionic polymer falls to no lessthan 50% of a concentration of sulfonic-acid-derivatized groups at thesurface up to a distance from the surface of at least 100 microns, atleast 250 microns, at least 500 microns, at least 1000 microns, at least2500 microns, at least 5000 microns, at least 10000 microns, or more.

In certain aspects, at a depth of 100 microns, a concentration ofsulfonic-acid-derivatized groups in the ionic polymer may range from 0%to 5% to 10% to 25% to 50% to 75% to 90% to 95% to 100% of a surfaceconcentration of the sulfonic-acid-derivatized groups.

in certain aspects, ionic polymers as described herein, including any ofthe ionic polymers described above, may have a thickness ranging fromabout 2 mm to 3 mm to 4 mm to 5 mm to 7.5 mm to 10 mm or more.

In certain aspects, the present disclosure pertains to interpenetratingpolymer networks and semi-interpenetrating polymer networks thatcomprise ionic polymers as described herein, including any of the ionicpolymers described above. Such interpenetrating polymer networks andsemi-interpenetrating polymer networks may, for example, have athickness ranging from about 2 mm to 3 mm to 4 mm to 5 mm to 7.5 mm to10 mm or more.

In certain aspects, the present disclosure pertains to methods offorming ionic polymers as described herein and interpenetrating andsemi-interpenetrating polymer networks that comprise ionic polymers asdescribed herein.

In certain aspects, the present disclosure pertains to implants,including orthopedic implants, that are formed from ionic polymers asdescribed herein and from interpenetrating and semi-interpenetratingpolymer networks that comprise ionic polymers as described herein.

In certain aspects, the present disclosure pertains to packaged productsthat contain implants, including orthopedic implants, that are formedfrom ionic polymers as described herein and interpenetrating andsemi-interpenetrating polymer networks that comprise ionic polymers asdescribed herein. In various embodiments, the implants are at leastpartially immersed in a divalent-cation-containing solution comprisingwater and one or more divalent metal cations, Thedivalent-cation-containing solution may be, for example, a simulatedbody fluid that contains physiologic levels of ions found in the bodyfluids such as synovial fluid or blood serum or cerebrospinal fluid. Incertain embodiments, the divalent-cation-containing solution maycomprise 0.1 to 5 mM total divalent metal cations. The concentration oftotal divalent cations in a solution is the combined concentration ofall divalent cations in the solution. (For example, if one liter ofsolution contains 0.5 millimole of calcium cations, 0,5 millimole ofmagnesium cations, and no other divalent cations, then that solutioncontains 1.0 mM total divalent cations.) in certain embodiments, thedivalent-cation-containing solution may comprise calcium ions, magnesiumions or a combination of calcium ions and magnesium ions. For instance,the divalent-cation-containing solution may comprise 0.5 to 5.0 mMcalcium ions, typically 0.5 to 2.0 mM calcium ions, more typically 0.8to 1.6 mM calcium ions, and in some embodiments 1.1 to 1.3 mM calciumions, among other possibilities and/or the divalent-cation-containingsolution may comprise 0.2 to 1.5 mM magnesium ions, typically 0.3 to 1.0mM magnesium ions, and in some embodiments, 0.5 to 0.7 mM magnesiumions, among other possibilities, In certain embodiments, thedivalent-cation-containing solution may further comprise monovalentmetal ions selected from sodium ions, potassium ions, or a combinationof sodium and potassium ions, in which case thedivalent-cation-containing solution may contain 0 to 300 mM totalmonovalent metal cations, among other possibilities. In variousembodiments, the ionic polymer comprises carboxylic acid groups,sulfonic acid groups, or a combination of carboxylic acid groups andsulfonic acid groups as described elsewhere herein.

In various embodiments, the implants comprise an interpenetrating orsemi-interpenetrating polymer network that comprises a first polymericnetwork comprising a first polymer and a second polymeric networkcomprising an ionic polymer as described elsewhere herein.

In various embodiments, the implants may be selected from a hip implant,a knee implant, a shoulder implant, hand implant, a toe implant, oranywhere else in the body where desired to replace cartilage, asdescribed elsewhere herein. In some embodiments, the implant isconfigured to repair or replace cartilage in a joint in the body, suchas a knee joint, a condyle, a patella, a tibial plateau, ankle joint, anelbow joint, a shoulder joint, a finger joint, a thumb joint, a glenoid,a hip joint, an intervertebral disc, an intervertebral facet joint, alabrum, a meniscus, a metacarpal joint, a metatarsal joint, a toe joint,a temporomandibular joint, or a wrist joint, and any portion thereof.

In certain aspects, the present disclosure pertains to implants,including orthopedic implants such as those described elsewhere herein,which maintain dimension and mechanical properties under divalentconditions.

In certain aspects, the present disclosure pertains to implants,including orthopedic implants such as those described elsewhere herein,which maintain water content (Le., within a range of ±5 wt %, preferably±2 wt %, more preferably ±1 wt %,) throughout a physiologic range ofdivalent ion concentrations found in living organisms, includingsynovial fluid of living organisms, particularly mammals, moreparticularly human beings.

In certain aspects, the present disclosure pertains to implants,including orthopedic implants such as those described elsewhere herein,which demonstrate an absolute % weight change per mM change in totaldivalent cation concentration of less than 10%, less than 5%, less than3%, less than 2%, or even less than 1% (ideally demonstrating nomeasurable weight change), for example, demonstrating such propertiesover a total divalent cation concentration range of from about 0.1 mM toabout 5 mM, including a total divalent cation concentration ranging fromhypo-physiological divalent cation levels of 1.4 mM (0.96 mM Ca²⁺,0.48mM Mg²⁺) to hyper-physiological divalent cation levels of 2.2 mM(1.44 mM Ca²⁺, 0.72 mM Mg²⁺).

In certain aspects, the present disclosure pertains to implants,including orthopedic implants such as those described elsewhere herein,which maintain a coefficient of friction of less than 0.1, preferablyless than 0.075, more preferably less than 0.05, over a total divalentcation concentration range of about 0.1 mM to about 5 mM. including overa physiologic total divalent cation concentration range of about 1.4 mM(0.96 mM Ca²⁺, 0.48mM Mg²⁺) to about 2.2 mM (1.44 mM Ca²⁺, 0.72 mMMg²⁺).

The present disclosure includes processes for modifying commoncommercially available hydrophobic thermoset or thermoplastic polymers,such as polyurethanes or acrylonitrile, butadiene styrene (ABS) toprovide novel materials with new properties, such as increased strength,lubricity, electrical conductivity and wear-resistance. Varioushydrophobic thermoset or thermoplastic polymers are described below. Thedisclosure also includes IPN and semi-IPN compositions as well asarticles made from such compositions and methods of using such articles.The IPN and semi-IPN compositions of this disclosure may attain one ormore of the following characteristics: high tensile and compressivestrength; low coefficient of friction; high water content andswellability; high permeability; biocompatibility; and biostability.

Applications of the present disclosure include the creation ofhydrophilic, lubricious articles and coatings to reduce the static anddynamic coefficient of friction between two bearing surfaces and toreduce biofilm formation and/or barnacle formation in marine vessels,other water crafts or water-borne objects, or pipes. Furthermore,applications of the present disclosure include electrochemicalapplications that require conduction of electrical current, orpermeability of ions such as proton exchange membranes, fuel cells,filtration devices, and ion-exchange membranes. In addition, the presentdisclosure can be used as a method for making bearings and moving partsfor applications such as engines, pistons, or other machines or machineparts. The present disclosure can also be used in numerous biomedicalapplications including cartilage substitutes, orthopedic jointreplacement and resurfacing devices or components thereof,intervertebral discs, stents, vascular or urinary catheters, condoms,heart valves, vascular grafts, and both short-term and long-termimplants in other areas of the body, such as skin, brain, spine, thegastro-intestinal system, the larynx, and soft tissues in general. Inaddition, the present disclosure can be used as a component of varioussurgical tools and instruments. In various applications drugs can beincorporated into the materials of the present disclosure for localizeddrug delivery, including drug delivery vehicles in which a therapeuticagent is released from a polymer matrix.

As previously noted, in certain aspects, the present disclosure pertainsto ionic polymers that comprise a combination of underivatizedcarboxylic acid groups and sulfonic-acid-derivatized groups, includingamino-sulfonic carboxylic acid groups, and methods of forming the same.

Sulfonic acid functional groups may be incorporated into an alreadyformed solid article (i.e., in a solid state, including porous andnon-porous articles) comprising a precursor polymer that comprisescarboxylic acid groups. In some embodiments, the sulfonic acidfunctional groups may be incorporated into an already formed IPN orsemi-IPN (including a gradient IPN or semi-IPN) that comprisescarboxylic acid groups. The general principle is to replace thecarboxylic acid groups present on a poly(carboxylic acid), for example,on a poly(acrylic acid) or poly (methacrylic acid) in an IPN withsulfonic acid-containing functional groups, among other possibilities.In some embodiments, methods are provided which comprise reacting (a) asolid article comprising a precursor polymer that comprises carboxylicacid groups with (h) a sulfonic-acid-containing compound (e.g., byreacting the carboxylic acid groups of the solid article with an aminosulfonic acid compound such that an amide bond is formed between thecarboxylic acid groups of the precursor polymer and the amine groups ofthe amino sulfonic acid compound).

In certain embodiments, a hydrophilic-hydrophobic IPN as presented in US20131/0138210, hereby incorporated by reference, which containscarboxylic, acid groups (e.g., carboxylate ionic groups) can besulfonated by means of amidation using an amine containing sulfonic acid(i.e., an amino sulfonic acid). An amide (peptide) bond is formedbetween carboxylates of the IPN and the amine in the sulfonic acid.

In some embodiments, the amino sulfonic acid compound is a compound ofthe formula (H₂N)_(x)R(SO₃H)_(y) or a salt thereof, where R an organicmoiety, where x is a positive integer, and wherein y is a positiveinteger. In certain embodiments, x may range from 1 to 10, typically, 1to 5 (i.e., x may be 1, 2, 3, 4 or 5) and y may range from 1 to 10,typically, 1 to 5 (i.e., y may be 1, 2, 3, 4 or 5). In some embodiments,the compound of the formula (H₂N)_(x)R(SO₃H)_(y) has a hydrodynamicradius that allows the diffusion of the molecule within the IPN. R maybe, for example, hydrocarbon moiety, for example, a including linear,branched or cyclic hydrocarbon moiety, or a hydrocarbon moiety having acombination of two or more of linear, branched and cyclic hydrocarbonsubstituents. The hydrocarbon moiety may be, for example, C1-C12hydrocarbon or a polymeric moiety including polymeric/oligomericcontaining heteroatoms. In certain embodiments, the hydrocarbon moietymay be selected from an alkane moiety, an alkene moiety, an alkyne,moiety, an aromatic moiety, or a hydrocarbon moiety having a combinationof two or more of alkane, alkene, alkyne or aromatic substituents. Incertain embodiments, the amino sulfonic acid may be selected fromtaurine,

and taurine derivatives, including 1-substituted, 2-substituted,1,1-substituted, 2,2-disubstituted, and 1,2-disubstituted taurines, suchas 1-hydrocarbon-substituted, 2-hydrocarbon-substituted,1,1-hydrocarbon-disubstituted, 2,2-hydrocarbon-disubstituted, and1,2-hydrocarbon-disubstituted taurines, where the substitutedhydrocarbons may be selected, for example, from the hydrocarbon moietiesdescribed above in other embodiments, the amino sulfonic acid compoundis one that results in the formation of 2-acrylamido-2-methyl propanesulfonic acid or acrylamido ethane sulfonic acid.

In various embodiments, the methods comprise contacting the solidarticle comprising the precursor polymer having carboxylic acid groupswith the sulfonic-acid-containing compound such that thesulfonic-acid-containing compound (e.g., an amino sulfonic acidcompound) is diffused into the solid article.

In various embodiments, the methods further comprise contacting thesolid article comprising the precursor polymer having carboxylic acidgroups with a coupling reagent such that the coupling reagent isdiffused into the solid article, thereby activating reactive groups(e.g., carboxylic acid groups) within the solid. article and promotingreaction with the sulfonic-acid-containing compound (e.g., by promotingthe formation of amide bonds between carboxylic acid groups of aprecursor polymer within the solid article and amine groups of the aminosulfonic acid. In these embodiments, the coupling reagent may bediffused into the solid article before the sulfonic-acid-containingcompound is diffused into the solid article, the coupling reagent may bediffused into the solid article after the sulfonic-acid-containingcompound is diffused into the solid article, or the coupling reagent andthe sulfonic-acid-containing compound may be diffused into the solidarticle simultaneously. Examples of coupling reagents includetriazine-based coupling reagents, as well as carbodiimide, phosphoniumand aminium salts, organophosphorus reagents, and fluoroformamidiniumcoupling reagents. In particular embodiments, the coupling reagent maybe a carbodiimide coupling reagent selected from1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC),1,3-bis(2,2-dimethyl-1,3-dioxolan-4-ylmethyl)carbodiimide (BDDC), and1-cyclohexyl-3-[2-morpholinoethyl]carbodiimide. In particularembodiments, the coupling reagent may be a triazine-based coupling agentselected from derivatives of 2,4,6-trichloro-1,3,5-triazine including2,4-dichloro-6-methoxy-1,3,5-triazine (DCMT),2-chloro-4,6,-dimethoxy-1,3,5-triazine (CDMT), its derivative withN-methylmorpholine (NMM),4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride(DMTMM). As discussed in more detail below, applicant has found that, byemploying suitable coupling agents, including triazine-based couplingreagents, under suitable conditions, sulfonic-acid-derivatized groupsmay be incorporated into the solid article comprising the precursorpolymer having carboxylic acid groups at depths that range from a fewmicrons to hundreds of microns or throughout the whole depth of thematerial. In various embodiments, the depth to which thesulfonic-acid-derivatized groups extend can be increased by repeatingthe reaction with the sulfonic-acid-containing compound.

The precursor polymer having carboxylic acid groups may be, for example,a homopolymer or copolymer (e.g., an alternating copolymer, randomcopolymer, gradient copolymer, block copolymer. etc.). The precursorpolymer having carboxylic acid groups may be selected, for example, frompolymers comprising one or more monomers selected from acrylic acid,methacrylic acid, crotonic acid, linolenic acid, maleic acid, andfumaric acid, among others.

In various embodiments, the solid article may comprise aninterpenetrating or semi-interpenetrating polymer network that comprisesa first polymeric network comprising a first polymer and a secondpolymeric network comprising the precursor polymer having carboxylic,acid groups. The first polymer may be, for example, a hydrophobicpolymer. The first polymer may be, for example, a thermoplastic orthermoset polymer. In various embodiments described herein, the firstpolymer may be a hydrophobic thermoplastic or thermoset polymer. Incertain beneficial embodiments, the first polymer may be hydrophobicthermoplastic polyurethane, such as a hydrophobic thermoplasticpolyether urethane, among others.

in some embodiments, the present disclosure pertains to an IPN orsemi-IPN (also referred to herein for convenience as a “mixed anion IPNor semi-IPN”) that comprises (a) a first polymeric network comprising afirst polymer and (b) a second polymeric network comprising acrosslinked ionic polymer that comprises sulfonic-acid-derivatizedgroups. For example, the first polymer may comprise a first polymer asdescribed elsewhere herein, and the ionic polymer may comprise acombination of underivatized carboxylic acid groups andsulfonic-acid-derivatized carboxylic acid groups. As another example,the first polymer may comprise a first polymer as described elsewhereherein, and the ionic polymer may comprise a combination ofunderivatized carboxylic acid groups, sulfonic-acid-derivatizedcarboxylic acid groups, and uncharged groups. As another example, thefirst polymer may comprise a first polymer as described elsewhereherein, and the ionic polymer may comprise a combination ofsulfonic-acid-derivatized carboxylic acid groups, optional unchargedgroups, and negligible or no underivatized carboxylic acid groups (e.g.,due to the conversion of all or essentially all of the underivatizedcarboxylic acid groups).

In some embodiments, the first polymer is a hydrophobic thermoset orthermoplastic polymer and the mixed anion IPN or semi-IPN exhibits alower coefficient of friction than the hydrophobic thermoset orthermoplastic polymer. In some embodiments, the mixed anion IPN orsemi-WN is more water-swellable, exhibits higher resistance to creep,and/or exhibits a higher conductivity and permeability than thehydrophobic thermoset or thermoplastic polymer. Some embodiments of thecomposition also include an anti-oxidation agent.

In some embodiments, the mixed anion IPN or semi-IPN is formed bydiffusing monomers comprising carboxylic-acid-group-containing monomersinto the first polymer (e.g., a hydrophobic thermoset or thermoplasticpolymer) and polymerizing the monomers to form a precursor polymercomprising carboxylic acid groups. Subsequently, asulfonic-acid-containing compound is diffused into the IPN or semi-IPNand a portion of the carboxylic acid groups in the precursor polymer isderivatized as described elsewhere herein, thereby providing an ionicpolymer that comprises a combination of underivatized carboxylic acidgroups and sulfonic-acid-derivatized carboxylic acid groups. Thesulfonic-acid-containing compound may be, for example, an amino sulfonicacid of the formula (H₂N)_(x)(SO₃H)_(y) as described above.

In particular embodiments, the mixed anion IPN or semi-IPN may comprisebetween 15 and 40% w/w, even more particularly, between 25 and 30 of theionic polymer.

In particular embodiments, between 10 and 40% mol %, even moreparticularly, between 21 and 31 mol % of a total quantity ofunderivatized carboxylic acid groups and sulfonic-acid-derivatizedcarboxylic acid groups in the mixed anion IPN or semi-IPN (referred toherein as “the total quantity”) are sulfonic-acid-derivatized carboxylicacid groups and between 90 and 60 mol %, even more particularly between79 and 69 mol % of the total quantity are underivatized carboxylic acidgroups.

In some embodiments, the mixed anion IPN or semi-IPN also includeswater. In certain cases, the water which may form a hydration gradientfrom a first portion of the composition to a second portion of thecomposition. An electrolyte may be dissolved in the water.

In various embodiments, the hydrophobic thermoset or thermoplasticpolymer may be physically entangled or chemically crosslinked with theionic polymer (i.e., the polymer comprising a combination ofunderivatized carboxylic acid groups and sulfonic-acid-derivatizedcarboxylic acid groups).

In some embodiments, the hydrophobic thermoset or thermoplastic polymerhas ordered and disordered domains, and the ionic polymer may bedisposed in the disordered domains.

In various embodiments the hydrophobic thermoset or thermoplasticpolymer may be selected from the group consisting of polymethylmethacrylate, polydimethylsiloxane, acrylonitrile butadiene styrene,polymethylmethacrylate, and polyurethanes including polyether urethanes,polycarbonate urethanes, silicone polyether urethanes, and siliconepolycarbonate urethanes.

In various embodiments, the precursor polymer comprising underivatizedcarboxylic acid groups and the ionic polymer comprising a combination ofunderivatized carboxylic acid groups and sulfonic-acid-derivatizedcarboxylic acid groups may be formed from one or more monomers selectedfrom acrylic acid, methacrylic acid, crotonic acid, linolenic acid,maleic acid, and fumaric acid.

In various embodiments, an article formed from the ionic polymercomprising a combination of underivatized carboxylic acid groups andsulfonic-acid-derivatized carboxylic acid groups (e.g.,amino-sulfonic-acid-derivatized carboxylic acid groups) is provided inwhich a concentration of the underivatized carboxylic acid groups and aconcentration of the sulfonic-acid-derivatized carboxylic acid groupsare substantially constant.

In various embodiments, an article formed from the ionic polymercomprising a combination of underivatized carboxylic acid groups andsulfonic-acid-derivatized carboxylic acid groups is provided in which aconcentration of the underivatized carboxylic acid groups and/or aconcentration of the sulfonic-acid-derivatized carboxylic acid groups isrelatively constant throughout the article. For example, (a) an articlemay be provided in which a concentration of the underivatized carboxylicacid groups varies by most +/−10%, at most +/−5%, at most +/−2%, at most+/−1%, or even less, throughout the article and/or (b) an article may beprovided in which a concentration of the sulfonic-acid-derivatizedcarboxylic acid groups varies by at most +/−10%, at most +/−5%, at most+/−2%, at most +/−1% or even less, throughout the article.

In various embodiments, an article formed from the ionic polymercomprising a combination of underivatized carboxylic acid groups andsulfonic-acid-derivatized carboxylic acid groups is provided in which aconcentration of the underivatized carboxylic, acid groups and/or aconcentration of the sulfonic-acid-derivatized carboxylic, acid groupsvaries substantially within the article. For example, an article may beprovided in which (a) a concentration of the underivatized carboxylicacid groups within the article varies by at least +/−10%, at least+/−25%, at least +/−50%, at least +/−100%, at least +/−250%, at least+/−500%, at least +/−1000%, or more, between two points (i.e., twolocations) within the article (e.g., between a one surface of thearticle and an opposing surface of the article, between an exterior ofthe article and an interior of the article, etc.) and/or (b) aconcentration of the sulfonic-acid-derivatized carboxylic acid groupswithin the article varies by at least +/−10%, at least +/−25%, at least+/−50%, at least +/−100%, at least +/−250%, at least +/−500%, at least+/−1000%, or more, between two points within the article (e.g., betweena one surface of the article and an opposing surface of the article,between an exterior of the article and an interior of the article,etc.).

In various embodiments, an article formed from the ionic polymercomprising a combination of underivatized carboxylic acid groups andsulfonic-acid-derivatized. carboxylic acid groups is provided in whichthere is a gradient in a concentration of the underivatized carboxylicacid groups and/or a gradient in a concentration of thesulfonic-acid-derivatized carboxylic acid groups. In some of theseembodiments, the gradients may approximate the shape of a step function.For example, (a) an article may be provided in which a concentration ofthe underivatized carboxylic acid groups decreases with increasingdistance from at least one outer surface of the article decreasing by atleast 10%, at least 25%, at least 50%, at least 75%, at least 90% up to100% from the at least one outer surface of the article to an interiorpoint (i.e., an interior location) within the article, also referred toherein as a point in the bulk of the article), (b) an article may beprovided in which a concentration of the underivatized carboxylic acidgroups increases with increasing distance from at least one outersurface of the article (e.g., increasing by at least 10%, at least 20%,at least 50%, at least 100%, at least 200%, at least 500%, at least1000% or more from the at least one outer surface of the article to aninterior point within the article), (c) an article may be provided inwhich a concentration of the sulfonic-acid-derivatized carboxylic acidgroups within the ionic polymer decreases with increasing distance fromat least on outer surface of the article (e.g., decreasing by at least10%, at least 25%, at least 50% at least 75%, at least 90% up to 100%from the at least one outer surface of the article to an interior pointwithin the article), or (d) an article may be provided in which aconcentration of the sulfonic-acid-derivatized carboxylic acid groupswithin the ionic polymer increases with increasing distance from atleast on outer surface of the article (e.g., increasing by at least 10%,at least 20%, at least 50%, at least 100%, at least 200%, at least 500%,at least 1000% or more from the at least one outer surface of thearticle to an interior point within the article).

Absolute values of the molar ratio of the sulfonic-acid-derivatizedcarboxylic acid groups to the underivatized carboxylic acid groups atvarious points within the article may vary widely. The molar ratio ofthe sulfonic-acid-derivatized carboxylic acid groups to theunderivatized carboxylic acid groups at a given point within the articlemay range from 10000:1 or more (including infinity, where 100% of theunderivatized carboxylic acid groups are converted tosulfonic-acid-derivatized carboxylic acid groups) to 1:100 or less, Forexample, the molar ratio of the sulfonic-acid-derivatized carboxylicacid groups to the underivatized carboxylic acid groups at a given pointwithin the article may range from 100000:1 to 50000:1 to 25000:1 to10000:1 to 5000:1 to 2500:1 to 1000:1 to 500:1 to 250:1 to 100:1 to 50:1to 25:1 to 10:1 to 5:1 to 2.5:1 to 1:1 to 1:2.5 to 1:5 to 1:10 to 1:25to 1:50 to 1:100) (i.e., ranging between any two of the precedingratios).

Articles formed from the ionic polymer comprising a combination ofunderivatized carboxylic acid groups and sulfonic-acid-deactivatizedcarboxylic acid groups may be provided wherein a molar ratio of thesulfonic-acid-derivatized carboxylic acid groups to the underivatizedcarboxylic acid groups is relatively constant throughout the article, orwhere a molar ratio of the sulfonic-acid-derivatized carboxylic acidgroups to the underivatized carboxylic acid groups varies substantiallywithin the article.

In embodiments where an article formed from the ionic polymer comprisinga combination of underivatized carboxylic acid groups andsulfonic-acid-derivatized carboxylic acid groups is provided in which amolar ratio of the sulfonic-acid-derivatized carboxylic acid groups tothe underivatized carboxylic acid groups within the article isrelatively constant within the article the molar ratio may vary, forexample, by at most +/−10%, at most +/−5%, at most +/−2%, at most +/−1%,or less, throughout the article.

In embodiments Where an article formed from the ionic polymer comprisinga combination of underivatized carboxylic acid groups andsulfonic-acid-derivatized carboxylic acid groups is provided in which amolar ratio of the sulfonic-acid-derivatized carboxylic acid groups tothe underivatized carboxylic acid groups varies substantially within thearticle, there may be a variation in the molar ratio of thesulfonic-acid-derivatized carboxylic: acid groups to the underivatizedcarboxylic acid groups of at least +/−10%, at least +/−25%, at least+/−50%, at least +/−100%, at least +/−250%, at least +/−500%, at least+/−1000%, or more, between two points within the article (e.g., betweena one surface of the article and an opposing surface of the article,between an exterior of the article and an interior of the article,etc.). In some embodiments, there may be a gradient in a molar ratio ofthe sulfonic-acid-derivatized carboxylic acid groups to theunderivatized carboxylic acid groups within the article. For example, amolar ratio of the sulfonic-acid-derivatized carboxylic acid groups tothe underivatized carboxylic acid groups may increase between onesurface of the article and an opposing surface of the article orincrease between an exterior surface of the article and an interior ofthe article. As another example, a molar ratio of thesulfonic-acid-derivatized carboxylic acid groups to the underivatizedcarboxylic acid groups may decrease between one surface of the articleand an opposing surface of the article or decrease between an exteriorsurface of the article and an interior of the article.

In this regard, as noted above, the ionic polymer may be formed from anarticle comprising a precursor polymer that comprises underivatizedcarboxylic acid groups by diffusing a coupling reagent into the articleand by diffusing a sulfonic-acid-containing compound into the article,wherein the coupling reagent may be diffused into the solid articlebefore, after, or at the same time as, the sulfonic-acid-containingcompound is diffused into the article. Consequently, concentrationgradients for the underivatized carboxylic acid groups and for thesulfonic-acid-derivatized carboxylic acid groups within the resultingarticle may be independently adjusted and thus are commonly differentfrom one another. For example, in various embodiments, a molar ratio ofthe concentration of the sulfonic-acid-derivatized carboxylic acidgroups relative to the underivatized carboxylic acid groups may decreasewith increasing distance from an outer surface of the article into theinterior of the article.

A concentration gradient in sulfonic-acid-derivatized carboxylic acidgroups and/or underivatized carboxylic acid groups in an article may,for example, provide a stiffness and/or hydration gradient within thearticle.

Some embodiments include a second hydrophobic thermoset or thermoplasticpolymer which may be disposed in a layer separate from the firsthydrophobic thermoset or thermoplastic polymer or may be diffusedthroughout the first hydrophobic thermoset or thermoplastic polymer.

In some embodiments, a layer of another material is deposited onto onesurface of an article formed from the ionic polymer comprising acombination of underivatized carboxylic acid groups andsulfonic-acid-derivatized carboxylic acid groups during themanufacturing process as a coating. This material may be added, forexample, to the non-hydrated surface of an article containing a gradientionic polymer. The material may be a bonding agent or version of thebonding agent and is physically, chemically, or physicochernicallyadhered to the surface of the article formed from the ionic polymer, forexample, the non-hydrated surface of the article containing the gradientionic polymer. By having this material coating disposed on this surface,the strength of a bonding agent applied at a later time is enhanced. Insome embodiments, this strength is enhanced because the coating materialand the bonding agent are compositionally the same or similar. In otherembodiments, the coating is the same material as that at the surface ofthe article. In some embodiments, the coating is a different material—atleast in part—as the that at the surface of the article. The coating maybe a polymer, co-polymer, or polymer blend, and in one embodiment, is aco-polymer of polymethylmethacrylate and urethane dimethacrylate. Thecoating may be a thin coating that is applied during an implantmanufacturing process, and may be applied by a variety of meansincluding but not limited to spin-coating, spray-coating,vapor-deposition, solution casting, painting, and lithography. In otherembodiments, the surface of one side of the article is roughened byapplication of an organic solvent and/or mechanical means such as butnot limited to sanding, sand-blasting, lithography, and/orimpression-molding. In some embodiments, the coating is applied to theroughened surface. In other embodiments, the roughened surface existswithout any additional coating.

Another aspect of the disclosure provides a process for producing awater-swellable IPN or semi-IPN from an hydrophobic thermoset orthermoplastic polymer including the following steps: placing a liquidcomprising one or more carboxylic-acid-group-containing monomers (e.g.,made up of pure monomers or monomers in solution) in contact with asolid form of the hydrophobic thermoset or thermoplastic polymer;diffusing the one or more carboxylic-acid-group-containing monomers intothe thermoset or thermoplastic polymer; and polymerizing the one or morecarboxylic-acid-group-containing monomers to form an ionic polymercomprising carboxylic acid groups inside the thermoset or thermoplasticpolymer, thereby forming a precursor IPN or semi-IPN having carboxylicacid groups.

Subsequently, a liquid comprising one or more amino sulfonic acidcompounds is contacted with the precursor IPN semi-IPN having carboxylicacid groups such that the one or more amino sulfonic acid compoundsdiffuse into the precursor IPN or semi-IPN, under conditions such thatthe one or more amino sulfonic acid compounds react with carboxylic acidgroups of the precursor IPN or semi-IPN to form amide bonds, resultingin a mixed anion IPN or semi-IPN that contains underivatized carboxylicacid groups and amino-sulfonic-acid-derivatized carboxylic acid groups.For example, an amino sulfonic acid of the formula the amino sulfonicacid is a compound of the formula (H₂N),R(SO₃H)_(y) as discussed above,may be reacted with carboxylic acid groups,—COOH, within the precursorIPN or semi-IPN, to form —CONH(H₂N)_(x−1)R(SO₃H)_(y) groups. In variousembodiments, a liquid comprising coupling reagent is contacted with theprecursor IPN or semi-IPN prior to, at the same time, or after contactwith the liquid containing the one or more amino sulfonic acidcompounds, such that the coupling reagent reacts with the carboxylicacid groups, thereby activating the carboxylic acid groups for amidebond formation with the one or more amino sulfonic acid compounds.

Some embodiments include the step of swelling the mixed anion IPN orsemi-IPN with water, e.g., to form a hydration gradient from a firstportion of the composition to a second portion of the composition. Themethod may also include the step of swelling the mixed anion IPN orsemi-IPN with an electrolyte solution.

In some embodiments, the hydrophobic thermoset or thermoplastic polymeris selected from polyurethane, polymethyl methacrylate,polydimethylsiloxane, acrylonitrile butadiene styrene andpolymethylmethacrylate, polyether urethane, polycarbonate urethane,silicone polyether urethane, and silicone polycarbonate urethanes amongothers. The carboxylic-acid-group-containing monomer solution used toform the ionic polymer comprising carboxylic acid groups inside thethermoset or thermoplastic polymer may be selected from acrylic acidmonomers, methacrylic acid monomers, crotonic acid monomers, linolenicacid monomers, maleic acid monomers, and fumaric acid monomers, amongother monomers comprising carboxylic acid groups.

Some embodiments include the step of changing the precursor IPN orsemi-IPN or mixed anion WN or semi-IPN from a first shape to a secondshape, such as by heating the precursor IPN semi-IPN or mixed anion IPNor semi-IPN.

Yet another aspect of the disclosure provides a medical implant (e.g.,an orthopedic implant, etc.) including a water-swellable mixed anion IPNor semi-IPN including a hydrophobic thermoset or thermoplastic polymerand an ionic polymer comprising a combination of underivatizedcarboxylic acid groups and sulfonic-acid-derivatized carboxylic acidgroups, the implant having a bone contacting surface shaped to conformto a bone surface. Some embodiments also include a fluid capsuledisposed in an interior region of the implant. Some embodiments have aninsertion portion adapted to be inserted into a bone and a jointinterface portion adapted to be disposed within a joint space, such asbone screws, sutures, or staples engaged with the mixed anion IPN orsemi-IPN and adapted to engage the bone to attach the mixed anion IPN orsemi-IPN to the bone and/or a stem extending from the bone contactsurface and adapted to be inserted into the bone. The medical implantmay also be incorporated as a bearing component of another device, suchas a metal-based prosthesis.

The medical implant may also include a bonding agent adapted to attachthe medical implant to a bone, such as a bone ingrowth surface formed onthe bone contact surface. In some embodiments, the ionic polymercomprising a combination of underivatized carboxylic acid groups andsulfonic-acid-derivatized carboxylic acid groups forms a concentrationgradient from a first portion of the implant to a second portion of theimplant. Some embodiments have a second hydrophobic thermoset orthermoplastic polymer adjacent to the first hydrophobic thermoset orthermoplastic polymer, the ionic polymer comprising a combination ofunderivatized carboxylic acid groups and sulfonic-acid-derivatizedcarboxylic acid groups interpenetrating at least the first hydrophobicthermoset or thermoplastic polymer.

In some embodiments, implants formed from ionic polymers as describedherein, including implants containing water-swellable mixed anion IPNsor semi-IPNs as described herein, may have properties mimickingstiffness and lubricity properties of natural cartilage. In someembodiments, implants formed from ionic polymers as described herein,including implants containing water-swellable mixed anion IPNs orsemi-IPNs as described herein, may be adapted and configured to replacecartilage in a joint. For example, the implants may have a shapeselected from the group consisting of a cap, a cup, a plug, a mushroom,a cylinder, a stem, and a patch. The implant may be adapted to repair orreplace cartilage in a joint in the body, such as a knee joint includinga knee medial compartment joint, a patellofemoral joint, and a totalknee joint, a knee meniscus, a condyle, a patella, a tibial plateau,ankle joint, an elbow joint, a shoulder joint including a labial joint,a hand joint including a metacarpal joint, a finger joint, a thumbjoint, and a base of thumb joint, a glenoid, a hip joint including anacetabular joint, an intervertebral disc, vertebral joint, including anintervertebral facet joint, a labrum, a meniscus, a foot joint,including a metatarsal joint and a toe joint, a jaw joint, including atemporomandibular joint, or a wrist joint and any portion thereof.

In some embodiments, the implants described herein may have at least aportion of the implant that is configured to transiently deform duringimplant placement in a joint.

Still another aspect of the disclosure provides a method of repairing anorthopedic joint including the steps of replacing natural cartilage witha water-swellable mixed anion WN or semi-IPN in accordance with thepresent disclosure, including engaging the mixed anion IPN or semi-IPNwith a bone surface defining the joint. The method may also include thesteps of bonding, suturing, stapling, and/or screwing the mixed anion.IPN or semi-IPN to the bone surface. The method may also includeincorporating the material as a bearing component of another device,such as a metal-based prosthesis. The method may also include the stepof inserting a stem portion into the bone surface. The orthopedic jointmay be selected from a group consisting of a shoulder joint including alabial joint, a hip joint including an acetabular joint, a wrist joint,a finger joint, a hand joint, including a metacarpal joint,, a thumbjoint, a base of thumb joint, an ankle joint, elbow joint, a foot joint,including a metatarsal joint and a toe joint, a jaw joint, including atemporomandibular joint, a knee medial compartment joint, apatellofemoral joint, a total knee joint, a femoral joint, an acetabularjoint, an elbow, an intervertebral facet, and a vertebral joint,including an intervertebral facet joint.

Yet another aspect of the disclosure provides a marine hull coatingincluding a water-swellable mixed anion IPN or semi-IPN in accordancewith the present disclosure, the coating having a hull contact surfaceadapted to attach to a marine hull. The coating may also include anultraviolet light protection agent anchor an anti-oxidation agent.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic illustration of a process of forming an IPN orsemi-IPN according to one aspect of this present disclosure. From leftto right: the thermoplastic material in this aspect of this presentdisclosure is polyurethane that is converted to a semi-IPN ofpolyurethane and poly(acrylic acid). Then the carboxylic moieties arederivatized to sulfonic moieties.

FIG. 2 is a schematic illustration of a sulfonation process according toone aspect of this present disclosure. The poly(acrylic acid) of thesemi-WN is reacted with taurine and(4-4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride) inbasic conditions to derive the poly(sulfonic acid) derivative ofpoly(acrylic acid) and taurine.

FIGS. 3A-3F illustrate divalent percent weight loss of sulfonated (FIG.3A-E) and non-sulfonated (FIG. 3E) gradient poly(etherurethane)-poly(acrylic acid) (PEU-PAA) test articles across a range ofPAA/PEU percentages as a function of the total divalent ionconcentration: (FIG. 3A) 17.6% PAA/PEU, (FIG. 3B) 22.2% PAA/PEU, (FIG.3C) 25.5% PAA/PEU, (FIG. 3D) 27.6% PAA/PEU, (FIG. 3E) 40.7% PAA/PEU,(FIG. 3F) non-sulfonated gradient PEU-PAA test article with 40.7%PAA/PEU. For all test articles made with different amount of PAA/PEUpercentage a line was fitted to derive the percent weight loss permillimolar total divalent ion concentration and the slope is indicate onthe top of each sub-figure. Error bars represent standard error; n=5 foreach point, NS: p<0.1,

FIG. 4 is a graph of normalized sulfonate peak intensity of Ramanmicroscopy spectra as a function of depth (mm) for a sulfonated gradientPEU-PAA in accordance with the present disclosure. Top: represents theintensity map of the ratio of the breathing mode of —SO₃ (1045 cm⁻¹)over one of the breathing modes of polyurethane (1640 cm⁻¹) throughoutthe depth (2 mm) of the sulfonated gradient PEU-PAA material, Bottom:Cumulative distribution of the ratio of the breathing mode of —SO₃ (1045cm⁻¹) over one of the breathing modes of polyurethane (1640 cm⁻¹) over200 um of thickness as a function of depth of the material.

DETAILED DESCRIPTION OF THE DISCLOSURE

The present disclosure includes processes for modifying commoncommercially available hydrophobic thermoset or thermoplastic polymersto confer upon them qualities such as lubricity, permeability,conductivity and wear-resistance. Such hydrophobic polymers ordinarilydo not soak up water and are generally useful for their mechanicalstrength, impermeability and insulating ability. An exemplary list ofhydrophobic polymers modifiable by the process of this disclosureincludes the following: Acrylonitrile butadiene styrene (ABS),Polymethylmethacrylate (PMMA), Acrylic, Celluloid, Cellulose acetate,Ethylene-Vinyl Acetate (EVA), Ethylene vinyl alcohol (EVAL), Kydex, atrademarked acrylic/PVC alloy, Liquid Crystal Polymer (LCP), Polyacetal(POM or Acetal), Polyacrylates (Acrylic), Polyacrylonitrile (PAN orAcrylonitrile), Polyamide (PA or Nylon), Polyamide-imide (PAI),Polyaryletherketone (PAEK or Ketone), Polyhydroxyalkanoates (PHAs),Polyketone (PK), Polyester, Polyetheretherketone (PEEK), Polyetherimide(PEI), Polyethersulfone (PES)—see Polysulfone, Polyethylenechlorinates(PEC), Polyimide (PI), Polymethylpentene (MP), Polyphenylene oxide(PPO), Polyphenylene sulfide (PPS), Polyphthalamide (PPA), Polystyrene(PS), Polysulfone (PSU), Polyvinyl acetate (PVA), Polyvinyl chloride(PVC), Polyvinylidene chloride (PVDC), Spectralon, Styrene-acrylonitrile(SAN), Polydimethylsiloxane (PDMS), and Polyurethanes (PU). A widevariety of polyurethanes can be used with varying hard segment, softsegment, and chain extender compositions, as will be described herein.

One aspect of the disclosure takes advantage of a characteristic of somemodifiable thermoset or thermoplastic hydrophobic polymers: the presenceof ordered and disordered (amorphous) domains within the polymer. Forexample, some hydrophobic thermoset or thermoplastic polymers such aspolyurethanes are phase-separated, containing first domains of hardsegments and second domains of soft segments, with the two domainsexhibiting different solubility properties with respect tointerpenetration of monomers. In polyurethanes, the hard segments aredisposed primarily within the ordered domains and the soft segments aredisposed primarily within the disordered (amorphous) domains. (Thestarting polymer may contain more than two domains, of course, withoutdeparting from the scope of the disclosure.) This difference inproperties between the two domains of the phase-separated polymerenables the process of this disclosure to impart new properties to thepolymer that can extend throughout the hulk of the material orthroughout only a portion of the material, e.g., in a particular regionor in a gradient. For example, a non-lubricious polymer can he madelubricious; an otherwise non-conductive polymer can be made conductive;and an otherwise non-permeable polymer can be made permeable. Moreover,the process can be performed repeatedly to introduce more than one newproperty to the starting polymer.

In some embodiments, phase separation in the polymer allows fordifferential swelling of one or more separated phases within the polymerwith, e.g., a solvent and/or monomer, which is then used to impart newproperties. According to the disclosure, for example, lubriciousness canbe introduced to an otherwise non-lubricious material by adding andpolymerizing one or more carboxylic-acid-group-containing monomers,followed by reaction with one or more sulfonic-acid-containingcompounds. In one embodiment, a polymer material with high mechanicalstrength and a lubricious surface can be made from an otherwisenon-lubricious, hydrophobic polymer. By converting otherwise hydrophobicmaterials into multi-phasic materials with both solid and liquid (water)phases, the present disclosure addresses a need in the art forlubricious, high strength materials for use in medical, commercial, andindustrial applications.

In some embodiments, a thermoplastic polyurethane-based polymercontaining a network of hard segments and soft segments may be swollenwith monomer and optional solvent, along with an initiator andcross-linker, such that the soft segments are swollen while mostly notaffecting the hard segment material. This swelling process is notdissolution of the polymer; rather, the hard segments act as physicalcrosslinks to hold the material together as the soft segments areimbibed with the monomer(s) and optional solvent(s). Afterpolymerization and cross-linking of the monomers and after reaction witha sulfonic-acid-containing compound, a second network is formed in thepresence of the first network, creating an IPN or semi-IPN in which thesecond polymer the polymerized and sulfonated monomer) is primarilysequestered within the soft, amorphous domain of the first polymer.Despite sonic degree of molecular rearrangement and further phaseseparation, the hard segments largely remain ordered and crystalline,providing structure and strength to the material.

The new properties provided by this IPN depend on the properties of thepolymerized monomers that were introduced and on thesulfonic-acid-containing compounds that are subsequently introduced.Examples of such new properties include, lubriciousness, conductivity,hardness, absorbency, permeability, photoreactivity and thermalreactivity. After optional swelling in a buffered aqueous solution, thesecond network of the mixed anion IPN or semi-IPN is ionized, and themixed anion IPN or semi-IPN is water-swollen and lubricious. Thus,hydrophilicity (Le., water absorbency) can be introduced into anotherwise hydrophobic material. A hydrophobic polymer material such aspolyurethane or ABS can be infiltrated with various mixed anion polymers(polymers comprising a combination of underivatized carboxylic acidgroups and amino-sulfonic-acid-derivatized carboxylic acid groups) suchthat it absorbs water.

In addition to absorbency, various levels of permeability (water, ion,and/or solute transport) can be introduced into an otherwisenon-permeable material. For example, a hydrophobic polymer material suchas polyurethane or ABS can be infiltrated with a mixed anion polymer sothat it absorbs water, as described above. This hydration of the bulk ofthe material allows for the transport of solutes and ions. The transportof solutes and ions and permeability to water is made possible by phasecontinuity of the hydrated phase of the mixed anion IPN der semi-IPN.This may be useful in various applications, including drug delivery,separation processes, proton exchange membranes, and catalyticprocesses, The permeability can also be utilized to capture, filter, orchelate solutes as a liquid flows over or through the material.Furthermore, because of this permeability, the materials of the presentdisclosure can be bestowed with increased resistance to creep andfatigue relative to their component hydrophobic polymers due to theirability to re-absorb fluid after sustained or repetitive loading.

Also, any of the domains can he doped with any number of materials, suchas antioxidants, ions, ionomers, contrast agents, particles, metals,pigments, dyes, biomolecules, polymers, proteins and/or therapeuticagents. Any of these materials can be incorporated physically orchemically (e.g., covalently bonded into or otherwise included as one ormore of the constituents of the IPN or semi-IPN).

The hydrophobic thermoset or thermoplastic polymer can be additionallycrosslinked or copolymerized with the carboxylic-acid-group-containingpolymer if, for example, acryloxy, methacryloxy, acrylamido, allylether, or vinyl functional groups are incorporated into one end or bothends of the thermoset or thermoplastic polymer and then cured by UV ortemperature in the presence of an initiator. For instance, apolyurethane dimethacrylate or polyurethane bisacrylamide can be used inthe first network by curing in the presence of a solvent (such asdimethylacetamide) and then evaporating the solvent. The addition ofchemical crosslinks (rather than just physical crosslinks) to the IPNadds a level of mechanical stability against creep or fatigue caused bycontinuous, dynamic loading.

In addition, in the case where the thermoplastic polymer is apolyurethane, a multi-arm (multifunctional) polyol or isocyanate can beused to create crosslinks in the polyurethane. In this case, a fullyinterpenetrating polymer network is created (rather than asemi--interpenetrating polymer network). The result is a compositematerial with the high strength and toughness of polyurethane and thelubricious surface and multi-phasic bulk behavior of the ionic polymer.Alternatively, other crosslinking methods can be used, including but notlimited to gamma or electron-beam irradiation. These features useful forbearing applications such as artificial joint surfaces, or as morebiocompatible, thrombo-resistant, long-term implants in other areas ofthe body such as the vascular system or the skin. Being swollen withwater also allows imbibement with solutes such as therapeutic agents ordrugs for localized delivery to target areas of the body.

In another embodiment of the present disclosure, the hydrophobicthermoset or thermoplastic polymer can be linked to thecarboxylic-acid-group-containing polymer. For example, polyurethane canbe linked through a vinyl-end group. Depending on the reactivity ratiobetween the end group and the monomer being polymerized, different chainconfigurations can be yielded. For instance, if the reactivity of themonomer with itself is much greater than the end group with the monomer,then the carboxylic-acid-group-containing polymer will be almostcompletely formed before the addition to the chain. On the other hand,if the reactivity of the monomer and the end group are similar, then arandom grafting-type copolymerization will occur. The monomers and endgroups can be chosen based on their reactivity ratios by using a tableof relative reactivity ratios published in, for example, The PolymerHandbook. The result of these will be a hybridcopolymer/interpenetrating polymer network.

Any number or combinations of ethylenically unsaturated monomers ormacromonomers (Le., with reactive double bonds/vinyl groups) can be usedalone or in combination with various solvents and selectively introducedinto one or more of the phases of the polymer as long as at least aportion of such monomers contain carboxylic acid functional groups.Other monomers include but are not limited to dimethylacrylamide,acrylamide, N-isopropylacrylamide (NIPAAm), methyl acrylate, methylmethacrylate, hydroxyethyl acrylate/methacrylate.

In one embodiment, a preformed, thermoplastic polymer may be immersed inacrylic acid (or in a solution of acrylic acid (1%-100%) or other vinylmonomer solution) along with crosslinker (e.g., triethylene glycoldimethacrylate or N,N′-methylene bisacrylamide) and photoinitiator (e.g.2-hydroxy-2-methyl propiophenone). The acrylic acid solution can bebased on water, salt buffer, or organic solvents such asdimethylacetamide, acetone, ethanol, methanol, isopropyl alcohol,toluene, dichloromethane, propanol, dimethylsulfoxide, dimethylformamide, or tetrahydrofuran. The polymer may be swollen by the monomer(e.g., due to solvation of the soft segments in the polymer). Themonomer content in the swollen polymer can range from as little as about1% to up to about 90%.

It is noted that although various aspects of the disclosure areillustrated herein using acrylic acid as an exemplary monomer, it shouldbe understood that various monomers having carboxylic acid groups arealso contemplated, including one or more of the following, among others:acrylic acid, methacrylic acid, crotonic acid, linolenic acid, maleicacid, and fumaric acid. Similarly, it is noted that although variousaspects of the disclosure are commonly illustrated herein using polyacrylic acid) as an exemplary polymer, it should be understood thatpolymers of various monomers having carboxylic acid groups may also beapplicable, including one or more of the following, among others:acrylic acid, methacrylic acid, crotonic acid, linolenic acid, maleicacid, and fumaric acid.

The monomer-swollen polymer may then be removed, placed in a mold madeof glass, quartz, or a transparent polymer, then exposed to UV light (orelevated temperature) to initiate polymerization and crosslinking of themonomers. Alternatively, instead of using a mold, the monomer-swollenpolymer can be polymerized while fully or partially exposed to air or aninert atmosphere (e.g., nitrogen or argon), or alternatively in thepresence of another liquid such as an oil (e.g., paraffin, mineral, orsilicone oil). Depending on the initiator used, exposure to UV light,IR, or visible light, a chemical, electrical charge, or elevatedtemperature leads to polymerization and crosslinking of thecarboxylic-acid-group-containing monomers within the hydrophobicpolymer. As an example, monomers (e.g. acrylic acid) are polymerized toform an ionic polymer comprising carboxylic acid groups within apreformed thermoplastic, hydrophobic matrix, forming an interpenetratingpolymer network (“IPN”). Solvents can be extracted out by heat andconvection or by solvent extraction. Solvent extraction involves the useof a different solvent (such as water) to extract the solvent frompolymer, while heat or convection relies upon evaporation of thesolvent.

Sulfonation of the IPN may then be conducted through an amidationreaction of carboxylic, acid groups with an amino sulfonic acid compoundsuch as taurine using4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride asthe catalyst.

Swelling of the mixed anion IPN or semi-IPN in aqueous solution such asphosphate buffered saline (or other salt solution such as the divalentcation solutions described elsewhere herein) at neutral pH will lead toionization of the carboxylic acid and sulfonic acid groups and furtherswelling with water and salts. The resulting swollen mixed anion IPN orsemi-IPN will have a lubricious surface conferred by the hydrophilic,charged polymer and high toughness and mechanical strength conferred bythe thermoplastic. In the case of a polyurethane-based mixed anion IPNor semi-WN, the mixed anion IPN or semi-IPN will have a structure inwhich crystalline hard segments in the polyurethane act as physicalcrosslinks in the first network, while chemical crosslinks will bepresent in the second network.

The materials can also be crosslinked after synthesis using gammaradiation or electron beam radiation. In one example,polyurethanelpolyacrylic acid can be synthesized and then crosslinked bygamma irradiation, for instance with doses of, for example, 5, 10, 15,20, or 25 kGy. In this case, the polymerization of polyacrylic acidwould be done in the absence of a crosslinker, and after formation ofthe polymer blend (physical IPN), the material would be exposed to gammaradiation. It is known in the art that crosslinking of poly(acrylicacid) hydrogels using gamma irradiation shows a dose-dependence to thecrosslinking of the polymer. In the case of the polyurethanes, thepolyurethane polymer can be a commercially available material, amodification of a commercially available material, or be a new material.

Any number of chemistries and stoichiometries can be used to create thepolyurethane polymer. For the hard segment, isocyanates used are 1,5naphthalene diisocyanate (NDI), isophorone isocyanate (IPDI),3,3-bitoluene diisocyanate (TODI), methylene bis (p-cyclohexylisocyanate) (H₁₂MDI), cyclohexyl diisocyanate (CHDI), 2,6 tolylenediisocyanate or 2,4 toluene diisocyanate (TDI), hexamethyl diisocyanate,or methylene bis(p-phenyl isocyanate). For the soft segment, chemicalsused include, for example polyalkylene oxides, such as polyethyleneoxide (PEO), polypropylene oxide (PPO), polybutylene oxide (PBO),polybutadiene, polydimethylsiloxane (PDMS), polyethylene adipate,polycaprolactone, polytetramethylene adipate, polyisobutylene,polyhexamethylene carbonate glycol, poly (1,6 hexyl 1,2-ethyl carbonate.Any number of telechelic polymers can be used in the soft segment, ifend-groups that are reactive with isocyanates are used. For instance,hydroxyl- or amine-terminated poly(vinyl pyrrolidone),dimethylacrylamide, carboxylate or sulfonated polymers, telechelichydrocarbon chains (with hydroxyl and/or amine end groups),dimethylolpropionic acid. (DMPA), or these in combination with eachother or with other soft segments mentioned above (e.g., PDMS) can beused.

Chain extenders include, for example, 1,4-butanediol, ethylene diamine,4,4′-methylene bis (2-chloroaniline) (MOCA), ethylene glycol, and hexanediol. Any other compatible chain extenders can be used alone or incombination. Crosslinking chain extenders can he used containingisocyanate-reactive end groups (e.g. hydroxyl or amine) and avinyl-based functional group (e.g. vinyl, methacrylate, acrylate, allylether, or acrylamide) may be used in place of some or all of the chainextender. Examples include 1,4-dihydroxybutene and glycerolmethacrylate. Alternatively, crosslinking can be achieved through theuse of a polyol such as glycerol which contains greater than twohydroxyl groups for reaction with isocyanates.

in some embodiments, at least 1% of the monomers in the second networkcomprise carboxylic acid groups. In one such embodiment, poly(acrylicacid) (PAA) hydrogel is used as the second polymer network, foamed froman aqueous solution of acrylic acid monomers, Othercarboxylic-acid-group-containing monomers include, for example,methacrylic acid. These other monomers can also be in a range of 1%-99%in either water or organic solvent, or may be in pure (100%) form. Oneembodiment of the monomer used to form the second network can bedescribed by the following characteristics: (1) it is capable ofswelling without dissolving the polyurethane, (2) capable ofpolymerizing, and (3) is carboxylic-acid-group-containing.

Other embodiments use an additional co-monomer which may be non-ionic,such as acrylamide, methacrylamide, N-hydroxyethyl acrylamide,N-isopropylacrylamide, methylmethacrylate, N,N-Dimethylacrylamide,N-vinyl pyrrolidone, 2-hydroxyethyl methacrylate, 2-hydroxyethylacrylate or derivatives thereof.

Any type of compatible cross-linkers may be used to crosslink the secondnetwork in the presence of any of the aforementioned first networks suchas for example, ethylene glycol dimethacrylate, ethylene glycoldiacrylate, diethylene glycol dimethacrylate (or diacrylate),triethylene glycol dimethacrylate (or diacrylate), tetraethylene glycoldimethacrylate (or diacrylate), polyethylene glycol dimethacrylate, orpolyethylene glycol diacrylate, methylene bisacrylamide,N,N′-(1,2-dihydroxyethylene) bisacrylamide, derivatives, or combinationsthereof. Any number of photoinitiators can also be used depending ontheir solubility with the precursor solutions/materials. These include,but are not limited to, 2-hydroxy-2-methyl-propiophenone and2-hydroxy-1-[4-(2-hydroxyethoxy) phenyl]-2-methyl-1-propanone. Inaddition, other initiators such as benzoyl peroxide, 2-oxoglutaric acid,azobisisobutyronitrile, or potassium persulfate (or sodium persulfate)can be used. For instance, benzoyl peroxide is useful fortemperature-initiated polymerizations, while azobisisobutyronitrile andsodium persulfate are useful as radical initiators.

In another embodiment, a solvent can be used as a vehicle to delivermonomers that otherwise would not mix (or solubilize with) the polymerto one (or more) phases of the polymer. The solvent must be carefullychosen based on the specific qualities and phases of the polymer andmonomers. For instance, acetic acid is capable of swelling but does notdissolve many polyurethanes. Therefore, acetic acid can be used to carryother monomers such as an acrylamide solution, that otherwise would notenter polyurethane, into the bulk of the polyurethane. This allows theacrylamide to be selectively polymerized inside one phase of thepolyurethane. The acetic acid can then be washed out leaving behind apolyurethane with one or more new properties. Other solvents that can beused include, but are not limited to, methanol, propanol butanol, (orany alkyl alcohol), acetone, dimethylacetamide, tetrahydrofuran, diethylether, or combinations of these. Taking into account the solubilities inthe phases of the polymer, solvents with varying degrees of swelling ofone can be chosen. Solubilities of the solvents and components of thematerial to be swollen can be obtained from polymer textbooks such asThe Polymer Handbook or can be measured experimentally.

After polymerization of the carboxylic-acid-group containing monomers,any optional co-monomers and any cross-linkers, the resultingcomposition is then reacted with one or more sulfonic-acid-containingcompounds to sulfonate a portion of the carboxylic-acid-group containingmonomers to complete the second network. In certain embodiments, thesulfonation of a precursor IPN or semi-IPN having carboxylic acid groupsis accomplished through an amidation reaction with taurine using4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride asthe catalyst. The chemical reaction process to create the mixed anionIPN or semi-WN is depicted in FIG. 1. The sulfonation chemistry used toconvert the carboxylic acid groups to sulfonate groups is shown in FIG.2. Of course, the process is not limited to PAA but is also applicableto virtually any polymer containing carboxylic acid groups.

Among the applications of the disclosure are the creation ofhydrophilic, lubricious sidings or coatings to reduce biofilm formationand/or barnacle formation in marine vessels, other water crafts orwater-borne objects, or pipes. In addition, the disclosure can be usedas a method for making bearings and moving parts for applications suchas engines, pistons, or other machines or machine parts. The disclosurecan also be used in artificial joints systems or long-term implants inother areas of the body, such stents and catheters for the vascular orurinary system or implants, patches, or dressings for the skin.

The present disclosure can be used to create a composition gradientwithin a starting homogenous polymeric material. A gradient can beformed in material along a thickness direction, with the mixed anion IPNor semi-IPN formed on one side and extending in a diminishingconcentration to another side, e.g., substantially only the startingpolymeric material. The mixed anion IPN or semi-IPN concentrationgradient may be radial within material, with the outer surface being thehighest concentration of mixed anion IPN or semi-IPN and the center orcore having the lowest concentration of mixed anion IPN or semi-IPN. Inone method of fabricating a thermoplastic gradient mixed anion IPN orsemi-IPN according to the present disclosure, one side of thethermoplastic material is imbibed with a monomer solution along with aphotoinitiator and a crosslinker, and then the monomer is polymerizedand crosslinked (e.g., with UV light) within the thermoplastic to form agradient mixed anion IPN or semi-IPN. In one embodiment, a mixed anionIPN or semi-IPN can be created in a gradient hydrophobic polymer isswollen in carboxylic-acid-containing monomer on one side only or if theswelling time is limited such that diffusion of the monomers through thebulk of the hydrophobic polymer is not complete. This is especiallyuseful in the creation of osteochondral grafts for orthopedic jointreplacement materials. For instance, in the case of a cartilagereplacement material, one side of the material is made lubricious andwater swollen, while the other remains a solid (pure thermoplastic).Alternatively, bulk materials with a mixed anion IPN or semi-IPN outeraspect and hydrophobic-polymer-only “core” can be made if the diffusionof carboxylic-acid-containing monomer into the hydrophobic polymer isprecisely controlled by timing the infiltration of the monomers into thebulk. The differential swelling that results from this configuration canlead to remaining stresses (compressive on the swollen side, tensile onthe non-swollen side) that can help enhance the mechanical and fatiguebehavior of the material. In the case of a material with a thicknessgradient, the base of hydrophobic-polymer-only material can be used foranchoring, adhering, or suturing the device to the anatomical region orinterest. This base can be confined to a small area or be large (e.g., askirt) and can extend outward as a single component or multiplecomponents (e.g., straps). The internal stresses built up within thethermoplastic during processing or after swelling can be reduced bytemperature-induced annealing. For instance, temperatures of 60-120degrees Celsius may be used for various times (30 minutes to many hours)to anneal the polymer, and the heat can he applied in an oven, by a hotsurface, by radiation, or by a heat gun. The thermoplastic can later becrosslinked using, for example, gamma or electron beam radiation.

Articles made from the mixed anion IPN's and semi-IPN's of thisdisclosure may also be formed in a laminate structure. In one example,the mixed anion IPN or semi-IPN structure is comprised of a hydrophilicpolymer such as sulfonated poly (acrylic acid) (sPAA) that isinterpenetrating a first thermoplastic such as polyether urethane, whichis formed on top of a second thermoplastic such as polycarbonateurethane. The first and second thermoplastics can be themselvescomprised of multiple layers of various hardnesses and properties. Inaddition, many more than two thermoplastic layers can he used, and oneor more of the thermoplastics can be crosslinked. Finally,non-thermoplastic elements can be incorporated into this construct.

Heat can be used to re-anneal the physical crosslinks in the polymer(e.g., the hard segments in the polyurethane) in the hydrophobic-polymerside of the gradient mixed anion IPN or semi-IPN to lead to differentdesired curvatures after bending (e.g., over a mold or template) andcooling, including both convex and concave curvatures on thehydrophobic-polymer side of the gradient mixed anion IPN or semi-IPN.Other shapes may be formed, of course, as desired. The use ofthermoplastic as a hydrophobic polymer facilitates molding of a deviceto a desired shape by, for example, injection molding, reactiveinjection molding, compression molding, or alternatively, dip-casting.The molded device can then be subjected to subsequent networkinfiltration and polymerization steps to yield the new mixed anion IPNor semi-IPN material.

Shaping of mixed anion IPN and semi-IPN articles according to thisdisclosure may be performed in situ, such as within a human body, forexample, by heating of a thermoplastic mixed anion IPN or semi-IPN toenable it to wrap around the curvature of a femoral head or to enable itto adapt to the curvature of a hip socket.

Shaped or unshaped mixed anion IPN and semi-IPN articles made accordingto this disclosure may be attached to other surfaces. For example, abonding agent such as a solvent, cement, or glue can be used to attachthe thermoplastic gradient mixed anion IPN or semi-IPN article to asurface at a bonded interface. Addition of the solvent, for example,causes the material to dissolve locally, and after contact with asurface and drying of the solvent, the thermoplastic adheres to thesurface. This approach can be used to attach a gradient mixed anion IPNor semi-IPN to bone surfaces in joints. The bonding agent may be sterilein a disposable syringe in certain embodiments.

In specific embodiments, the bonding agent may comprise a urethanedimethacrylate and methyl methacrylate (MMA). The bonding agent may becured using radiation, such as visible light, infrared light, orultraviolet light using a photoinitiator; it may be cured using athermal initiator, chemical initiator or catalysts, and: or redoxactivated initiation systems, for example, one comprisingcamphorquinone, and N,N-Dimethyl-p-toluidine. A combination ofphoto-initiation and non-light-based initiation systems such as thermal,chemical, and/or redox systems may be used. An accelerating agent mayalso be used. The urethane dimethacrylate may comprise soft segmentsselected, for example, from polyalkylene oxides, such as polyethyleneoxide (PEO), polypropylene oxide (PPO), and polybutylene oxide (PBO),polybutadiene, polydimethylsiloxane (PDMS), polyethylene adipate,polycaprolactone, polytetramethylene adipate, polyisobutylene,polyhexamethylene carbonate glycol, and poly (1,6 hexyl 1,2-ethylcarbonate). The urethane dimethacrylate may comprise hard segmentsformed, for example, from 1,5 naphthalene diisocyanate (NDI), isophoroneisocyanate 3,3-bitoluene diisocyanate (TODI), methylene his(p-cyclohexyl isocyanate) (H₁₂MID), cyclohexyl diisocyanate, 2,6tolylene diisocyanate or 2,4 toluene diisocyanate (TDI), hexamethyldiisocyanate, or methylene bis(p-phenyl isocyanate), The urethanedimethacrylate component may comprise, for example, about 70-90% byweight of the bonding agent.

In general, in one embodiment, a system is provided including an articlecomprising a mixed anion IPN or semi-IPN of the present disclosure andan adhesive kit comprising a bonding agent. (e.g., such as a solvent,cement, or glue).

In general, in one embodiment, a packaged article is provided thatcomprises an article comprising a mixed anion IPN or semi-IPN inaccordance with the present disclosure. In some embodiments, adivalent-cation-containing solution comprising one or more divalentmetal cations is contained within the sterile package.

This and other embodiments can include one or more of the followingfeatures. The adhesive kit can include, a first reservoir including afirst mixture including at least one of a urethane dimethacrylateoligomer and a. methyl methacrylate monomer; at least one of aphotoinitiator and a thermal initiator; and an inhibitor; a secondreservoir including a second mixture including at least one of aurethane dimethacrylate monomer and a methyl methacrylate monomer; andan accelerator; and an instruction for use; wherein at least one of thefirst reservoir and the second reservoir can include a urethanedimethacrylate monomer and at least one of the first reservoir and thesecond reservoir can include a methyl methacrylate monomer.

Both the first reservoir and the second reservoir can include a urethanedimethacrylate monomer and a methyl methacrylate monomer. The secondreservoir can further include an inhibitor. The system can furtherinclude poly(methyl methacrylate). The system can further include athird reservoir including a poly(methyl methacrylate) powder. The firstmixture, the second mixture and the poly(methyl methacrylate) can definea component weight, and a weight of the poly(methyl methacrylate) powdercan include from about 1% to about 70% of the component weight. Thesystem can further include a polystyrene. The system can further includea photoinitiator and a thermal initiator. The first reservoir caninclude a first chamber in a syringe and the second reservoir caninclude a second chamber in the syringe, wherein the syringe can beconfigured to combine the first mixture with the second mixture tocreate an adhesive mixture. The system can further include a nozzleconnected with the syringe configured to dispense the adhesive mixture.The first reservoir and the second reservoir each can include from about0% (w/w) to about 100% (w/w), typically, from about 1% (w/w) to about99% (w/w), urethane dimethacrylate oligomer and/or 0% (w/w) to about100% (w/w), typically, from about 1% (w/w) to about 99% (w/w), methylmethacrylate. The first reservoir and/or the second reservoir each caninclude from about 0% (w/w) to about 100% (w/w), typically, from about1% (w/w) to about 99% (w/w), methyl methacrylate. The at least oneinitiator can include a photoinitiator including between 0% (w/w) andabout 5% (why), typically, from about 1% (why) to about 5% (w/w),camphorquinone. The at least one initiator can include a thermalinitiator including between 0% (w/w) and about 5% (w/w), typically, fromabout 1% (w/w) to about 5% (w/w), benzoyl peroxide. The accelerator caninclude between 0% (w/w) and about 5% (w/w), typically, from about 1%(w/w) to about 5% (w/w), N,N-dimethyl-p-toluidine. The inhibitor caninclude between 0% (w/w) and about 5% (w/w), typically, from about 1%(w/w) to about 5% (w/w), hydroquinone. The system can further include anadditive configured to prevent an infection. The system can furtherinclude an antibiotic. The system can further include a radiopaquematerial. The first mixture can define a viscosity between about 1 Pa·sand 5000 Pa·s.

In one embodiment, the adhesive kit can be comprised by a singlereservoir that contains from about 0% (w/w) to about 100% (w/w),typically, from about 1% (w/w) to about 99% (w/w), urethanedimethacrylate oligomer and/or 0% (w/w) to about 100% (w/w), typically,from about 1% (w/w) to about 99% (w/w), methyl methacrylate, from about0% (w/w) to about 100% (w/w), typically, from about 1% (w/w) to about99% (w/w), methyl methacrylate, an optional initiator (which caninclude, for example, at least one of a photoinitiator and a thermalinitiator), typically in an amount from about 0% (w/w) to about 5%(w/w), for example, from about 1% (why) to about 5% (w/w), and anoptional accelerator, typically in an amount from about 0% (\v/w) toabout 5% (w/w), for example, from about 1% (w/w) to about 5% (w/w), Thesingle reservoir can include a chamber in a syringe. The system canfurther include a nozzle connected with the syringe configured todispense the curable adhesive. The initiator can include aphotoinitiator including between 0% (w/w) and about 5% (w/w), typically,from about 1% (w/w) to about 5% (w/w), camphorquinone. The acceleratorcan include between 0% (w/w) and about 5% (w/w), typically, from about1% (w/w) to about 5% (w/w), N,N-dimethyl-p-toluidine. The inhibitor caninclude between 0% (w/w) and about 5% (w/w), typically, from about 1%(w/w) to about 5% (w/w), hydroquinone. The system can further include anadditive configured to prevent an infection. The system can furtherinclude an antibiotic. The system can further include a radiopaquematerial. The first mixture can define a viscosity between about 1 Pa·sand 5000 Pa·s.

The mixed anion and semi-IPN compositions of this disclosure, formed,e.g., by the methods of this disclosure, may be used in a variety ofsettings. One particular use is as artificial cartilage in anosteochondral graft. The present disclosure provides a bone-sparingarthroplasty device based on an interpenetrating polymer network thatmimics the molecular structure, and in turn, the elastic modulus,fracture strength, and lubricious surface of natural cartilage.Emulating at least some of these structural and functional aspects ofnatural cartilage, the mixed anion semi-IPNs and anion IPNs of thepresent disclosure form the basis of a novel, bone-sparing, “biomimeticresurfacing” arthroplasty procedure. Designed to replace only cartilage,such a device is fabricated as a set of flexible, implantable devicesfeaturing lubricious articular surfaces and osteointegrablebone-interfaces.

in principle, the device can be made for any joint surface in the body.For example, a device to cover the tibial plateau will require ananalogous bone-preparation and polymer-sizing process. For a device tocover the femoral head in the hip joint, a cap shaped device fits snuglyover the contours of the femoral head. For a device to line theacetabulum, a hemispherical cup-shaped device stretches over the lip andcan be snapped into place in the socket to provide a mating surface withthe femoral head. In this way, both sides of a patient's hip joint canbe repaired, creating a cap-on-cap articulation. However, if only one ofthe surfaces is damaged, then only one side may be capped, creating acap-on-cartilage articulation. in addition, the materials of the presentdisclosure can be used to cap or line the articulating surfaces ofanother joint replacement or resurfacing device (typically comprised ofmetal) to serve as an alternative bearing surface.

To create a cap-shaped device using the present disclosure for theshoulder joint (also a ball-and-socket joint), a process similar to thatof the hip joint is used. For instance, a shallow cup can be created toline the inner aspect of the glenoid. Furthermore, devices for otherjoints in the hand, fingers, elbow, ankles, feet, and intervertebralfacets can also be created using this “capping” concept. In oneembodiment in the distal femur, the distal femur device volume followsthe contours of the bone while sparing the anterior and posteriorcruciate ligaments.

The mixed anion IPN and semi-IPN of the present disclosure may be usedas a cartilage replacement plug in joints of the body where cartilagehas been damaged, as described below.

The mixed anion IPN and semi-IPN of this disclosure, made, for example,according to the methods of this disclosure, may be used as a fully orpartially synthetic osteochondral graft, The osteochondral graftconsists of a, lubricious, cartilage-like synthetic bearing layer thatmay be anchored to porous bone or a synthetic, porous bone-likestructure. The bearing layer has two regions: a lubricious surface layerand a stiff, bone anchoring layer. In one embodiment, the top,lubricious region of the bearing layer consists of an interpenetratingpolymer network that is composed of two polymers. The first polymer maybe a hydrophobic thermoplastic with high mechanical strength, includingbut not limited to polyether urethane, polycarbonate urethane, siliconepolyether urethane, and silicone polycarbonate urethanes, or thesematerials with incorporated urea linkages, or these materials withincorporated urea linkages (e.g. polyurethane urea). The second polymermay be a hydrophilic polymer derived fromcarboxylic-acid-group-containing monomers, including but not limited toacrylic acid, which are subsequently subjected to a sulfonation processin which the carboxylic-acid-group-containing monomers are reacted witha sulfonic-acid-containing compound. The bottom region of the bearinglayer (bone anchoring layer) may be a stiff, non-resorbablethermoplastic that can be caused to flow with ultrasonic weldingvibration, ultrasonic energy, laser energy, heat, RE energy andelectrical energy. The bone anchoring layer is used to anchor thebearing layer to bone or a bone-like porous structure. If porous bone isused, it can be cancellous bone from a human or animal, if a synthetichone-like material is used, it can consist of porous calcium-phosphate(and/or other materials, including but not limited to porous carbonatedapatite, beta-tricalcium phosphate, or hydroxyapatite), or a porousresorbable or non-resorbable thermoplastic as described above, includingbut not limited to polycarbonate urethane, polyether urethane, PLA,PLLA, PLAGA, and/or PEEK. The bearing layer is anchored to the porousbone or bone-like structure via application of pressure combined withenergy that cause the bone anchoring material to melt and flow into thepores or spaces of the bone or bone-like structure, after which theenergy source is removed and the material re-solidifies. The energysource can include but is not limited to vibration, ultrasonic energy,laser energy, heat, RE energy, and electrical energy.

In various embodiments, the compositions of the present disclosure canbe used to form a device to partially or completely resurface damagedjoints in the body of mammals (animals or human). These devices can befixated to hone through any number of means, such as a press-fit, screws(metal or plastic, either resorbable or nonresorbable), sutures(resorbable or nonresorbable), glue, adhesives, light-curable adhesives(e.g. polyurethane or resin-based), or bonding agent (such aspolymethylmethacrylate or calcium phosphate, or dental cements).

An osteochondral graft implant formed from a mixed anion IPN or semi-IPNof this disclosure can be used to replace or augment cartilage within ajoint, such as a hip or shoulder joint. The implant may be slipped overthe head of the humerus or femur. In sonic embodiments, the implant mayinclude an opening to accommodate a ligament or other anatomicalstructure.

Implants and other articles may be made in a variety of complex shapesaccording to the disclosure. For example, osteochondral grafts mayformed from a mixed anion IPN or semi-IPN of this disclosure that may beused singly or in any combination needed to replace or augment cartilagewithin a knee joint. For example, an osteochondral graft may be adaptedto engage the femoral condyles (or alternatively, just one condyle), maybe adapted to engage one or both sides of the tibial plateau, may beadapted to engage the patella and to articulate with an osteochondralgraft adapted to engage the patellofemoral groove and/or may be adaptedto engage the lateral and medial menisci.

Osteochondral grafts may also be used in other joints, such as in thefinger, hand, ankle, elbow, feet or vertebra. Labrum prosthesis may beformed from a mixed anion IPN or semi-IPN of this disclosure for use inreplacing or resurfacing the labrum of the shoulder or hip. A mixedanion IPN or semi-IPN of this disclosure may be used as a bursaosteochondral graft, labrum osteochondral graft, glenoid osteochondralgraft and humeral head osteochondral graft. In some embodiments, a mixedanion IPN or semi-IPN of this disclosure may be used as prostheses forresurfacing intervertebral facets.

The mixed anion IPN's and semi-IPN's compositions of this disclosure maybe formed as prosthetic cartilage plugs for partial resurfacing of jointsurfaces. For example, a prosthetic cartilage plug may be formed from agradient mixed anion IPN composition of this disclosure. Plug may have astem portion formed on a thermoplastic side of the article and adaptedto be inserted into a hole or opening in a hone. The head of the plug isformed to be a lubricious mixed anion IPN or semi-IPN, as describedabove. Stem may be press fit into a hole or opening in the bone, leavingthe lubricious mixed anion IPN surface to be exposed to act asprosthetic cartilage.

A prosthetic cartilage plug formed from the mixed anion IPN or semi-IPNof the present disclosure, in which the stem is provided with helicalridges to form a screw for fixation of the plug to bone.

Embodiments of the composition of this disclosure may be used to maketwo-side lubricious implants. Implants may be sized and configured toreplace an intervertebral disc. Implants may have lubricious mixed anionIPN or semi-IPN surfaces (formed, e.g., as described above) on its upperand lower sides. A knee spacer having a wedge-shaped cross-section maybe formed. As with disc prosthesis, spacer also has lubricious mixedanion IPN or semi-IPN surfaces on its upper and lower sides.

Other variations and modifications to the above compositions, articlesand methods are described below.

The hydrophobic polymer can be one that is available commercially orcustom-made and made by many ways extruded, injection molded,compression molded, reaction injection molded (RIM) or solution-casted.)The first polymer can be uncrosslinked or crosslinked by various means.Either polymer can be crosslinked by, e.g., gamma radiation or electronbeam radiation.

Any number or combinations of ethylenicaily unsaturated monomers ormacromonomers (e.g., containing reactive double bonds) can be used asthe basis of the second or subsequent network so long ascarboxylic-acid-group-containing monomers are included. These includebut are not limited those containing vinyl, acrylate, methacrylate,allyl ether, or acrylamide groups. And number of pendant functionalgroups can be conjugated to these ethylenically unsaturated groupsincluding but not limited to carboxylic acids, esters, alcohols, ethers,phenols, aromatic groups, or carbon chains.

The hydrophobic polymer may be a polyurethane-based polymer such as thefollowing: polyether urethane, polycarbonate urethane, polyurethaneurea, silicone polyether urethane, or silicone polycarbonate urethane.Other polyurethanes with other hard segments, soft segments, and chainextenders are possible.

Other polymers can be used as the hydrophobic polymer, such ashomopolymers or copolymers of silicone (polydimethylsiloxane) orpolyethylene.

When a polyurethane-based polymer is used as the hydrophobic polymer,the extent of physical and chemical crosslinking of thepolyurethane-based polymer can be varied between physicalcrosslinking-only (thermoplastic) to extensive chemical crosslinking. Inthe case of chemical crosslinking, the crosslinkable polyurethane can beused alone or as a mixture with thermoplastic (uncrosslinked)polyurethane.

The conditions of polymerization (i.e., ambient oxygen, UV intensity, UVwavelength, exposure time, temperature) and sulfonation may be varied.

The orientation and steepness of the composition gradients can be variedby various means such as time and/or method of immersion in the monomerand/or amino sulfonic acid compound, and the application of externalhydrostatic positive or negative pressure.

The hydrophobic polymer can be made porous by various techniques such asfoaming or salt-leaching. After swelling of the porous polymer (such asPU) with a monomer (such as AA) followed by polymerization or AA andreaction with an amino sulfonic acid, a porous mixed anion IPN isformed.

Additional layers of thermoplastics can be added to material on eitherthe IPN side or the thermoplastic side-only by curing or drying the newthermoplastic to the surface. The layers can all be the same material orbe different materials (e.g. ABS+polyurethane, polyetherurethane+polycarbonate urethane, etc.

A number of different solvents can be used during the synthesis of thepolyurethane, the second network, or both, including but not limited todimethylacetamide, tetrahydrofuran, dimethylformamide, ethanol,methanol, acetone, water, dichloromethane, propanol, methanol, orcombinations thereof.

Any number of coupling reagents may be employed to promote the reactionof the amino sulfonic acid compounds with thecarboxylic-acid-group-containing polymers, including triazine-basedcoupling reagents, carbodiimides, phosphonium and aminium salts andfluoraformamidinium coupling reagents in a particular embodiment, thecoupling reagent may be4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride(DMTMM).

The degree and depth of derivatization (i.e., sulfonation) of solidarticles comprising a precursor polymer having carboxylic acid groups,including PAA-based IPNs, depends on balancing the diffusion rate of thereactants with the reaction kinetics and hydrolysis rate of the couplingreagent and of the intermediate ester. One class of coupling reagentsthat has been used extensively for the activation and derivatization ofcarboxylic acids in aqueous solutions are carbodiimides. In variousembodiments, an amino sulfonic acid compound such as taurine isinitially diffused into a PAA-based IPN, followed by the addition of anN-substituted carbodiimide. N-substituted carbodiimides react withcarboxylic acids to form highly reactive, o-acylisourea intermediatesthat are pH dependent and tend to hydrolyze within seconds at nearphysiological pH (Hoare, DG and Koshland, DEJ. (1967) ‘A method for thequantitative modification and estimation of carboxylic acid groups inproteins’, Journal of Biological Chemistry, 242(10), pp. 2447-2453).After hydrolysis, the intermediate ester is converted back to thecarboxylic acid and an inactive N-acylurea. This immediate hydrolysis ineffect consumes the coupling reagent before it diffuses within the bulkof the IPN and react with the primary amine of the amino sulfonic acidcompound. Lowering the pH can reduce the hydrolysis rate of theintermediate ester, but the hydrolysis of the unreacted coupling reagentis accelerated in acidic conditions (Gilles, M. A., Hudson, A. Q. andBorders, C. L. (1990) ‘Stability of water-soluble carbodiimides inaqueous solution’, Analytical Biochemistry. Academic Press, 184(2), pp.244-248. Moreover, the diffusivity of the coupling reagent is reduced inacidic conditions as the IPN loses its water content and itspermeability is decreased. This results in further inhibition of thebulk reaction as the coupling reagents is consumed on the surface of theIPN. Taken together, molecules that are labile in aqueous solutions orform intermediate esters that are prone to hydrolysis at physiologic pHare not able to effectively derivatize the bulk of the PAA based IPN'sand the modification remains localized in the surface of the IPN.

Various properties of the IPNs in physiologic conditions, including thelubricious properties, are dependent on the bulk derivatization of thematerial. The present inventors have found that IPN modification beyonda certain depth can be achieved only if a) the coupling reagent is watersoluble and not liable in aqueous conditions, b) the intermediate esteris stable in physiologic pH, and c) the diffusion rate of the reactantsis adequate to allow the reaction to occur before the intermediate estergets hydrolyzed. Triazine based coupling reagents such as CDMT or DMTMM,are stable in aqueous conditions and have been used to derivatizemacro-sugars such as hyaluronan (D′este M, Eglin M, (2014), ‘Asystematic analysis of DMTMM vs EDC/NHS for ligation of amines toHyaluronan in water’, Carbohydrate Polymers, vol: 108 pp: 239-246).Reactions with DMTMM, where all the reactants are in solution, can havehigher conversion rate than carboiimides. In this embodiment, thereaction conditions can be tuned to allow the efficient diffusion of thereactants before the hydrolysis of the intermediate ester that is formedbetween the triazine-based compound and the carboxylic acid groups ofthe secondary network of the IPN. Since the reaction is rate limited bydiffusion and ester hydrolysis, the depth of the reaction can becontrolled by varying the pH, by varying the reaction time, by theaddition of the coupling reagent, or a combination any two or all threeof the foregoing. The pH allows one to control the permeability of theIPN and the reactivity/hydrolysis rate of the intermediate ester. Thereaction time allows one to control the amount of time needed forreactants to diffuse and react within the bulk of the material. Thecontrolled addition of the coupling reagent allows the coupling reagentto be added at the same rate as the overall reaction rate, whichcombines reagent diffusion and reaction together with hydrogel swelling.By adjusting these parameters the derivatization of the IPN may beachieved in depths that range from a few microns to hundreds of micronsor throughout the whole depth of the material.

Any number of initiators can be used such as photoinitiators (e.g.,phenone-containing compounds), thermal initiators, or chemicalinitiators. Examples of thermal initiators include but are not limitedto azo-compounds, peroxides (e.g., benzoyl peroxide), persulfates (e.g.,potassium persulfate or ammonium persulfate), derivatives, orcombinations thereof.

Variations of the crosslinking identity and density (e.g. 0.0001%-25% bymole crosslinking agent with respect to the monomer), initiatorconcentration (e.g. 0.0001%-0% by mole with respect to the monomer)molecular weight of precursor polymers, relative weight percent ofpolymers, light wavelength (UV to visible range), light intensity (0.01mW/cm²-5 W/cm²), temperature, pH and ionic strength of swelling liquid,and the level of hydration.

The second network material can be synthesized in the absence of acrosslinking agent.

The water content of these materials can range between 2% to 99%.

Different components of the mixed anion IPN can be incorporated incombination with carboxylic-acid-group-containing monomers, such asvinyl alcohol, ethylene glycol-acrylate, 2-hydroxyethylacrylate,2-hydroxyethylmethacrylate, acrylamide, N-isopropylacrylamide,dimethacrylamide, and combinations or derivatives thereof. Any monomeror combination of monomers can be used in conjunction with a suitablesolvent as long as a carboxylic-acid-group-containing monomer isincluded and are able to enter (swell) the first polymer.

The mixed anion IPN can have incorporated either chemically orphysically within its bulk or its surface certain additives such asantioxidants (e.g., Vitamin C, Vitamin E, or santowhite powder) and/oranti-microbial agents (e.g., antibiotics). These can be chemicallylinked to the material by, for example, esterification of theanti-oxidant with any vinyl-group containing monomer such asmethacrylate, acrylate, acrylamide, vinyl, or allyl ether.

More than two networks (e.g., three or more) can also be formed, each ofwhich are either crosslinked or uncrosslinked.

Other modifications will be apparent to those skilled in the art.

Further aspects of the present disclosure are shown in the paragraphs tofollow.

Aspect 1. An implant comprising an ionic polymer that comprisesunderivatized carboxylic acid groups and amino-sulfonic-acid-derivatizedcarboxylic: acid groups.

Aspect 2. The implant of aspect 1, wherein the underivatized carboxylicacid groups correspond to one or more of the following: underivatizedacrylic acid monomers within the ionic polymer, underivatizedmethacrylic acid monomers within the ionic polymer, underivatizedcrotonic acid monomers within the ionic polymer, underivatized linolenicacid monomers within the ionic polymer, underivatized maleic acidmonomers within the ionic polymer, and underivatized fumaric acidmonomers within the ionic polymer, and wherein theamino-sulfonic-acid-derivatized carboxylic acid groups correspond one ormore of the following: amino-sulfonic-acid-derivatized acrylic acidmonomers within the ionic polymer, amino-sulfonic-acid-derivatizedmethacrylic acid monomers within the ionic polymeramino-sulfonic-acid-derivatized crotonic acid monomers within the ionicpolymer, amino-sulfonic-acid-derivatized linolenic acid monomers withinthe ionic polymer, amino-sulfonic-acid-detivatized maleic acid monomerswithin the ionic polymer, and amino-sulfonic-acid-derivatized fumaricacid monomers within the ionic polymer.

Aspect 3. The implant of any of aspects 1-2, wherein the implantcomprises a measurable amount of an amino sulfonic acid compound of theformula (H₂N)_(x)R(SO₃H)_(y) or a salt thereof, where R is an organicmoiety, x is a positive integer and y is a positive integer.

Aspect 4. The implant of aspect 3, wherein R is a hydrocarbon moiety.

Aspect 5. The implant of aspect 4, wherein the hydrocarbon moiety is analkane moiety, an alkene moiety, an alkyne moiety, an aromatic moiety,or a hydrocarbon moiety having a combination of two or more of alkane,alkene, alkyne and aromatic substituents.

Aspect 6. The implant of any of aspects 4-5, wherein the hydrocarbonmoiety is a C1-C12 hydrocarbon moiety.

Aspect 7. The implant of any of aspects 1-2, wherein the implantcomprises a measurable amount of an amino sulfonic acid compoundselected from taurine and taurine derivatives.

Aspect 8. The implant of any of aspects 1-7, wherein a concentration ofthe underivatized carboxylic acid groups and a concentration of theamino-sulfonic-acid-derivatized carboxylic acid groups are substantiallyconstant throughout the implant.

Aspect 9. The implant of any of aspects 1-7, wherein a concentration ofthe underivatized carboxylic acid groups and/or a concentration of theamino-sulfonic-acid-derivatized carboxylic acid groups varies by atleast +/−10% between two points in the implant.

Aspect 10, The implant of any of aspects 1-7, wherein the implantcomprises a gradient in a concentration of the underivatized carboxylicacid groups and/or a gradient in a concentration of theamino-sulfonic-acid-derivatized carboxylic acid groups.

Aspect 11. The implant of aspect 10, wherein a concentration of theunderivatized carboxylic acid groups decreases with increasing distancefrom at least one outer surface of the implant.

Aspect 12. The implant of aspect 10, wherein a concentration of theunderivatized carboxylic acid groups increases with increasing distancefrom at least one outer surface of the implant.

Aspect 13, The implant of any of aspects 10-12, wherein a concentrationof the amino-sulfonic-acid-derivatized carboxylic acid groups decreaseswith increasing distance from at least one outer surface of the implant.

Aspect 14, The implant of any of aspects 10-12, wherein a concentrationof the amino-sulfonic-acid-derivatized carboxylic acid groups increaseswith increasing distance from at least one outer surface of the implant.

Aspect 15. The implant of any of aspects 1-14, wherein a molar ratio ofthe amino-sulfonic-acid-derivatized carboxylic acid groups to theunderivatized carboxylic acid groups varies by at least +1- 10% betweentwo points in the implant.

Aspect 16. The implant of any of aspects 1-14, wherein a molar ratio ofthe amino-sulfonic-acid-derivatized carboxylic acid groups to theunderivatized carboxylic acid groups decreases with increasing distancefrom at least on outer surface of the implant within the implant.

Aspect 17. Implant of any of aspects 1-14. wherein a molar ratio of theamino-sulfonic-acid-derivatized carboxylic acid groups to theunderivatized carboxylic acid groups increases with increasing distancefrom at least on outer surface of the implant within the implant

Aspect 18. The implant of any of aspects 1-14, wherein a molar ratio ofthe amino-sulfonic-acid-derivatized carboxylic acid groups to theunderivatized carboxylic acid groups varies between one surface of theimplant to and an opposing surface of the implant.

Aspect 19. The implant of any of aspects 1-18, Wherein the implantcomprises an interpenetrating or semi-interpenetrating polymer networkthat comprises a first polymeric network comprising a first polymer anda second polymeric network comprising the ionic polymer.

Aspect 20. The implant of aspect 19, wherein the first polymer ishydrophobic polymer.

Aspect 21. The implant of any of aspects 19-20, wherein the firstpolymer is a thermoplastic polymer,

Aspect 22, The implant of any of aspects 19-21, wherein the firstpolymer is a polyurethane.

Aspect 23. The implant of aspect 22, wherein the polyurethane is apolyether urethane.

Aspect 24. The implant of any of aspects 1-23, wherein the implant isconfigured to repair or replace cartilage in a joint in the body.

Aspect 25. The implant of aspect 24, wherein the joint in the body isselected from a knee joint, a condyle, a patella, a tibial plateau, anankle joint, an elbow joint, a shoulder joint, a finger joint, a thumbjoint, a glenoid, a hip joint, an intervertebral disc, intervertebralfacet joint, a labrum, a meniscus, a metacarpal joint, a metatarsaljoint, a toe joint, a temporomandibular joint, and a wrist joint,including portions thereof.

Aspect 26. A method comprising reacting a solid article comprising aprecursor polymer that comprises underivatized carboxylic acid groupswith an amino sulfonic acid compound such that an amide bond is formedbetween the carboxylic acid groups of the precursor polymer and theamine groups of the amino sulfonic acid compound.

Aspect 27. The method of aspect 26, wherein the amino sulfonic acidcompound is a compound of the formula (H₂N)_(x)(SO₃H)_(y) or a saltthereof, where R is an organic moiety, x is a positive integer and y isa positive integer.

Aspect 28, The method of aspect 26, wherein R is a hydrocarbon moiety.

Aspect 29. The method of aspect 28, wherein the hydrocarbon moiety is analkane moiety, an alkene moiety, an alkyne moiety and aromatic moiety,or a hydrocarbon moiety comprising a combination of two or more ofalkane, alkene, alkyne or aromatic substituents.

Aspect 30, The method of any of aspects 28-29, wherein the hydrocarbonmoiety is a C1-C12 hydrocarbon moiety.

Aspect 31. The method of aspect 26, wherein the amino sulfonic acid isselected from taurine and taurine derivatives.

Aspect 32, The method of any of aspects 26-31, comprising contacting thesolid article with the amino sulfonic acid compound such that the aminosulfonic acid compound is diffused into the solid article.

Aspect 33. The method of aspect 32, further comprising contacting thesolid article with a coupling reagent such that the coupling reagent isdiffused into the solid article.

Aspect 34. The method of aspect 33, wherein the coupling reagent isdiffused into the solid article before the sulfonic acid compound isdiffused into the solid article, wherein the coupling reagent isdiffused into the solid article after the sulfonic acid compound isdiffused into the solid article, or wherein the coupling reagent and thesulfonic acid compound are diffused into the solid articlesimultaneously.

Aspect 35. The method of any of aspects 33-34, wherein the couplingreagent is selected from a triazine-based coupling reagent, acarbodiimide, coupling reagent, a phosphonium salt coupling reagent, anaminium salt coupling reagent, and a fluoroformamidinium couplingreagent.

Aspect 36. The method of any of aspects 33-34, wherein the couplingreagent is 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholiniumchloride (DMTMM).

Aspect 37. The method of any of aspects 26-36, wherein the precursorpolymer selected from polymers comprising one or more monomers selectedfrom acrylic acid, methacrylic acid, crotonic acid, linolenic acid,maleic acid, and fumaric acid.

Aspect 38. The method of any of aspects 26-37, wherein the solid articlecomprises an interpenetrating or semi-interpenetrating polymer networkthat comprises a first polymeric network comprising a first polymer anda second polymeric network comprising the precursor polymer.

Aspect 39. The method of aspect 38, wherein the first polymer ishydrophobic polymer.

Aspect 40. The method of any of aspects 38-39, wherein the first polymeris a thermoplastic polymer.

Aspect 41. The method of any of aspects 38-40, wherein the first polymeris a polyurethane.

Aspect 42. The method of aspect 41, wherein the polyurethane is apolyether urethane.

Aspect 43. The method of any of aspects 26-42, wherein the implant isconfigured to repair or replace cartilage in a joint in the body.

Aspect 44. The method of aspect 43, wherein the joint in the body isselected from a knee joint, a condyle, a patella, a tibial plateau, anankle joint, an elbow joint, a shoulder joint, a finger joint, a thumbjoint, glenoid, a hip joint, an intervertebral disc, an intervertebralfacet joint, a labrum, a meniscus, a metacarpal joint, a metatarsaljoint, a toe joint, a temporomandibular joint, and a wrist joint,including portions thereof.

Aspect 45. An implant comprising an ionic polymer and adivalent-cation-containing solution comprising one or more divalentmetal cations, wherein the implant is at least partially immersed in thedivalent-cation-containing solution.

Aspect 46. The implant of aspect 45, wherein the implant and thedivalent-cation-containing solution are contained within a sterilepackage.

Aspect 47. The implant of any of aspects 44-46, wherein thedivalent-cation-containing solution is a simulated body fluid thatcontains physiologic levels of ions found in the synovial fluid.

Aspect 48. The implant of any of aspects 44-47, wherein thedivalent-cation-containing solution comprises 0.1 to 5 mM total divalentmetal cations.

Aspect 49. The implant of any of aspects 44-48, wherein thedivalent-cation-containing solution comprises calcium ions, magnesiumions or a combination of calcium and magnesium ions.

Aspect 50. The implant of any of aspects 44-48, wherein thedivalent-cation-containing solution comprises calcium ions and magnesiumions.

Aspect 51. The implant of aspect 50, wherein thedivalent-cation-containing solution comprises 0.5 to 2.0 mM calciumions,

Aspect 52. The implant of any of aspects 50-51, wherein thedivalent-cation-containing solution comprises 01 to 1.5 mM magnesiumions.

Aspect 53. The implant of any of aspects 44-52, wherein thedivalent-cation-containing solution further comprises monovalent metalions selected from sodium ions, potassium ions, or a combination ofsodium and potassium ions.

Aspect 54. The implant of aspect 53, wherein thedivalent-cation-containing solution contains 0 to 300 mM totalmonovalent metal cations.

Aspect 55. The implant of any of aspects 44-54, wherein the ionicpolymer comprises carboxylic acid groups, sulfonic acid groups, or acombination of carboxylic acid groups and sulfonic acid groups.

Aspect 56. The implant of any of aspects 44-54, wherein the ionicpolymer comprises carboxylic acid groups and sulfonic acid groups.

Aspect 57. The implant of any of aspects 44-56, wherein the implantcomprises an interpenetrating or semi-interpenetrating polymer networkthat comprises a first polymeric network comprising a first polymer anda second polymeric network comprising the ionic polymer.

Aspect 58. The implant of aspect 57, wherein the first polymer ishydrophobic polymer.

Aspect 59. The implant of any of aspects 57-58, wherein the firstpolymer is a thermoplastic polymer.

Aspect 60. The implant of any of aspects 57-59, wherein the firstpolymer is a polyurethane.

Aspect 61. The implant of aspect 60, wherein the polyurethane is apolyether urethane.

Aspect 62, The implant of any of aspects 44-61, wherein the implant isselected to repair or replace cartilage in a joint in the body.

Aspect 63. The implant of aspects 62, wherein the joint is selected froma knee joint, a condyle, a patella, a tibial plateau, an ankle joint, anelbow joint, a shoulder joint, a finger joint, a thumb joint, a glenoid,a hip joint, an intervertebral disc, an intervertebral facet joint, alabrum, a meniscus, a metacarpal joint, a metatarsal joint, a toe joint,a temporomandibular joint and a wrist joint, including portions thereof.

EXAMPLES Example 1

The following description refers to a first exemplary embodiment ofinterpenetrating ionic polymer compositions with polyether urethane asthe first network and polyacrylic acid as a second polymer network. TheIPN is synthesized sequentially in two steps: test articles made frompolyether urethane are impregnated in an aqueous solution of acrylicacid 70% (w/w %) which is supplemented with 5000 ppm andN-N′-methylenebis(acrylamide) and 1000 ppm2-hydroxy-2-methylpropiophenone. The swollen articles are polymerizedunder ultraviolet irradiation (40 mW/cm²) for 13 minutes and thenneutralized at constant pH=7.4. The final composition of the IPNcontained 37/19/45 (wt %) of PEU, PAA and H₂O, respectively. Testarticles are incubated in taurine (aminoethanesulfonic acid) solution(320 mM) for 1 day, after which an equimolar amount of DMTMM((4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methyl-morpholinium chloride)is added. The test articles are left to react for 48 h and they arewashed with copious amounts of water for 4 d. This process isillustrated schematically in FIG. 2. After synthesis the chemicalcomposition is assessed by elemental analysis (Table 1). The yield ofsulfonation of PAA was 50%. Moreover, as shown in FIG. 4, thepenetration of the amidation reaction reached halfway through (50%), or1000 microns, the overall thickness of the test article (i.e., a 2 mmthick sample). In other words, if both sides participate in thediffusion of the reagents then the conversation can reach 100% and thematerial will be functionalized throughout the thickness of the PAA-PEUnetwork. In contrast, when using a carbodiimide such as EDC underidentical reaction conditions and reactants ratios the penetration andfunctionalization of the PAA-PEU network did not exceed 20%, or 400microns in depth for a 2 mm thick sample. This difference in couplingefficiency between EDC and triazine coupling reagents has also beenreported previously in the functionalization of hyaluronan macropolymersin aqueous conditions (D'este, M, Eglin D, Alini Ni, (2014), ‘Asystematic analysis of DMTMM vs EDC/NHS for ligation of amines toHyaluronan in water’, Carbohydrate Polymers, vol: 108 pp: 239-246).

The following description refers to a second exemplary embodiment ofinterpenetrating ionic polymer compositions with polyether urethane asthe first network and polyacrylic acid as a second polymer network. TheIPN is synthesized sequentially in two steps: test articles made frompolyether urethane are impregnated in an aqueous solution of acrylicacid 60% (w/w %) which is supplemented with 5000 ppm andN-N′-methylenebis(acrylamide) and 1000 ppm2-hydroxy-2-methylpropiophenone. The swollen articles are polymerizedunder ultraviolet irradiation (40 mW/cm²) for 13 minutes and thenneutralized at constant pH=7.4. The final composition of the IPNcontained 48/17/35 (wt %) of PEU, PAA and H₂O, respectively. Testarticles are incubated in taurine solution (320 mM) for 1 day, afterwhich an equimolar amount of DMTMM is added. The test articles are leftto react for 48 h and they are washed with copious amounts of water for4 d. After synthesis the chemical composition is assessed by elementalanalysis (Table 1). The yield of sulfonation of PAA was 29%.

The following description refers to a third exemplary embodiment ofinterpenetrating ionic polymer compositions with polyether urethane asthe first network and polyacrylic acid as a second polymer network. TheIPN is synthesized sequentially in two steps: test articles made frompolyether urethane are impregnated in an aqueous solution of acrylicacid 50% (w/w %) whiCh is supplemented with 2000 ppm andN-N′-methylenebis(acrylamide) and 2000 ppm2-hydroxy-2-methylpropiophenone. The swollen articles are polymerizedunder ultraviolet irradiation (40 mW/cm²) for 13 minutes and thenneutralized at constant pH=7.4. The final composition of the IPN.contained 57/16/26 (wt PEU, PAA and H₂O respectively. Test articles areincubated in taurine solution (320 mM) for 1 day, after whiCh alaequimolar amount of DMTMM is added. The test articles are left to reactfor 48 h and they are washed with copious amounts of water for 4 d.After synthesis the chemical composition is assessed by elementalanalysis (Table 1). The sulfonation yield PAA was 26%.

TABLE 1 Composition of exemplary sulfonated ionic interpenetratingnetworks PEU/PAA/H₂O Yield (% (wt %) Conditions C H N S sulfonation)57/16/26 Control 60.72 6.63 4.72 N/A N/A 57/16/26 Reacted 60.00 6.865.85 1.51 26% with taurine 48/17/35 Control 59.26 6.40 4.38 N/A N/A48/17/35 Reacted 57.70 6.86 6.07 1.88 29% with taurine 37/19/45 Control56.35 5.98 3.86 N/A N/A 37/19/45 Reacted 54.27 6.53 6.24 3.94 50% withtaurine

Example 2

Gradient PEU-PAA formulations with a range of PAA/PEU (w/w %) contentfrom 17.6% to 29.9% were synthesized by following procedures along thelines described in Example 1. There is a linear correlation between theAA soaking solution and the PAA/PEU (w/w %), which allows determinationof the final PAA/PEU percentage based on the initial soaking solution.Results are shown in Table 2

TABLE 2 Test samples produced for sulfonation and testing AA % PEU PAAWater PAA/PEU (w/w)† (%) (%) (%) (w/w %) 45 68.10 12.0 19.9 17.6 5065.50 12.1 22.4 18.5 55 59.50 12.2 28.3 20.5 57 53.40 13.6 33.0 25.5 6053.1 14.5 32.5 27.3 63 49.2 14.2 36.6 28.9 65 48.1 14.4 37.4 29.9 7038.5 15.6 45.9 40.7 †AA % (w/w) refers to the percentage of Acrylic Acidin water used for the synthesis of the gradient PEU-PAA test articles.

The gradient PEU-PAA formulations were then sulfonated in accordancewith procedures along the lines of Example 1. The percent sulfonationwas characterized by dry and wet weight increase along with elementalanalysis to calculate sulfur content and sulfonation conversion. Thedata are summarized in Table 3. Sulfur content ranged from 0.5 to 2% andthe sulfonation conversion from 9% to 31%.

TABLE 3 Weight increase, sulfur content and sulfonation conversion forsulfonated gradient PEU-PAA Wet weight Dry weight Sul- Sulfonation AAPAA/PEU increase increase phur conversion (w/w %) (w/w %) (%) (%) (%)(%) 45 17.6  6.19 ± 1.21  6.06 ± 0.08 0.66 17 50 18.5 5.16 ± 0.5  5.15 ±0.96 0.73 14 55 20.5  9.65 ± 0.43  8.23 ± 1.71 0.5 9 57 25.5  8.29 ±0.54  9.11 ± 0.04 1.14 21 60 27.3 11.31 ± 0.74 11.28 ± 0.03 1.35 22 6328.9 11.37 ± 1.12 11.87 ± 0.76 1.41 27 65 29.9 15.31 ± 1.12 12.75 ± 0.221.66 31 70 40.7 16.77 ± 0.9  14.45 ± 2.55 1.64 11

The sulfonated gradient PEU-PAA materials exhibited a trend of higherweight increase after sulfonation with an increase in PAA/PEU w/w %,suggesting that with increasing PAA content, more carboxylic groups fromPAA react with the taurine to introduce sulfonate groups. The weightincrease (both wet and dry) for sulfonated gradient PEU-PAA was found tobe linear as a function of PAA/PEU content. The dry weight increase isbelieved to result from the addition of taurine molecules to the PAAbackbone via sulfonation reaction, while the wet weight increase isbelieved to result from the ability of sulfonated gradient PEU-PAA toretain water content.

Elemental analysis was performed to get the carbon, nitrogen, hydrogen,and sulfur contents from the sulfonated test articles. This data wasused to calculate the conversion of carboxylic groups into sulfonategroups. As seen from Table 3, the sulfur content/sulfonation conversionincreased with the increasing of PAA/PEU percentage. This indicates thatas the number of carboxyl group per unit weight increase, more taurinecould be attached.

The last synthesis step of sulfonated gradient PEU-PAA test articlesinvolved equilibrating in simulated body fluid (SBF, 1.2 mM Ca²⁺, 0.6 mMMg²⁺, 154 mM NaCl) before gamma irradiation. The final composition forall the synthesized materials after SBF equilibration were calculatedand listed in Table 4.

TABLE 4 Composition of sulfonated gradient PEU-PAA after equilibrationin SBF Sulfonated (Sulfonated AA PEU PAA + PAA Water PAA + PAA)/PEU (w/w%) (%) (%) (%) (w/w %) 45 65.7 16.7 17.6 25 50 62.2 18.3 19.5 29 55 57.318.8 23.9 33 57 51.7 20.5 27.8 40 60 50.9 23.0 26.1 45 63 46.7 22.3 31.048 65 44.5 22.8 32.7 51 70 34.9 23.7 41.4 68

Tensile, compressive, tear properties of sulfonated gradient PEU-PAAtest articles across a range of PAA content were evaluated. The data, issummarized in Tables 5 through 7. To allow for direct comparison of thematerial properties between gradient PEU-PAA formulations and anon-sulfonated gradient PELT-PAA formulation using a common variable,PAA/PEU percentage is used as the independent variable for the followingreasons: (a) the same sulfonation conditions were used across allsynthesized. materials irrespectively of their PAA/PEU (w/w %), (b)sulfonation was indirectly controlled by the level of PAA/PEU (w/w %)(see Table 3), and (c) material synthesized with the same initialconditions had statistically similar mechanical propertiesirrespectively of the sulfonation process or the sulfur content.

The tensile properties for all formulations are listed in Table 5 andTable 5.1. The Ultimate tensile strength (UTS) was found to decreasewith an increase in PAA/PEU w/w %. This is attributed to an increase inwater content as a function of PAA/PEU w/w % (Table 3) whiCh results inweaker materials.

TABLE 5 Tensile Strength of sulfonated gradient PEU- PAA andnon-sulfonated gradient PEU-PAA. Sulfonation Ultimate PAA/PEU conversionTensile Strength Formulation w/w % (%) (MPa) Sulfonated gradient 17.6 17 91.3 ± 10.5 PEU-PAA 22.2 14 78.7 ± 8.7 20.5 9 61.5 ± 6.5 25.5 21 54.8 ±7.7 27.2 22 40.7 ± 4.8 28.9 27 34.5 ± 3.7 30 31 33.8 ± 5.8 40.7 11 22.9± 1.2 Non-sulfonated gradient 40.7 N/A 50.2 ± 3.1 PEU-PAA

TABLE 5.1 Tensile properties of sulfonated gradient PEU-PAA andNon-sulfonated gradient PEU-PAA Ultimate Tangent tensile Tensile tensilePAA/PEU strain modulus modulus Formulation w/w % (%) (MPa) (MPa)Sulfonated 17.6 223.8 ± 52.3 37.1 ± 2.2 37.1 ± 2.2 gradient 22.2 189.8 ±51.1 37.8 ± 1.3 37.8 ± 1.3 PEU-PAA 20.5 169.7 ± 40.1 34.5 ± 1.1 34.5 ±1.1 25.5 153.0 ± 46.5 33.4 ± 1.4 33.4 ± 1.4 27.2 128.3 ± 31.5 32.2 ± 2.032.2 ± 2.0 28.9 110.6 ± 22.5 31.6 ± 2.0 31.6 ± 2.0 30 117.3 ± 50.7 29.5± 1.7 29.5 ± 1.7 40.7  95.2 ± 12.8 24.6 ± 0.5 24.6 ± 0.5 Non-sulfonated40.7 181.0 ± 32.7 29.0 ± 0.3 29.0 ± 0.3 gradient PEU-PAA

Similar trends were observed for all other tensile properties evaluated.Specifically, the ultimate true strain which captures the maximumelongation of the material before failure was reduced as a function ofthe PAA/PEU w/w %, ranging from 223.8±52.3% for the formulation with thelowest (17.6%) PAA/PEU w/w %, to 95.2±12.8% for the formulation withhighest (40.7%) (Table 5.1. The ultimate true strain of non-sulfonatedgradient PEU-PAA was 181.0±32.7%, which is almost 2 times higher thanthe sulfonated counterpart (95.2±12.8%) with the same PAA/PEU w/w %.This is attributed to the sulfonated gradient PEU-PAA formulation with40.7% PAA/PEU w/w % having more water (41.4%—see Table 3) than thenon-sulfonated gradient PEU-PAA (36.7%—see Table 3). Moreover, highvariance of the ultimate true strain was observed which is attributed tothe stochasticity of the material failure under tension which isaffected by material and test article imperfections.

The tensile modulus (Young's modulus) that defines the relationshipbetween stress and strain in the linear elastic region, decreasedexponentially as a function of increasing PAA/PEU w/w %. The tensilemodulus (32.5±0.8 MPa) for the formulation with the 40.7 (highest)PAA/PEU w/w % decreased significantly (p<0.01) from the previousformulation (48.4±2.8 MPa) with 30% PAA/PEU w/w%, which suggests thatabove this threshold the tensile modulus drops rapidly. Moreover,similar to the trends seen in ultimate tensile strength and tensilestrain, the tensile modulus of the non-sulfonated gradient PEU-PAA, washigher (46.4±2.3) than the sulfonated gradient PEU-PAA with the samePAA/PEU w/w %.

Similar to UTS, the tangent tensile modulus at 30% strain (see Table5.1), which is useful in describing the behavior of a material that hasbeen stressed beyond the elastic region and reaches plastic deformation,decreased with increasing PAA/PEU w/w %. The tangent tensile modulus was37.1±2.2 MPa for test articles with lowest (17.6%) PAA/PEU w/w % and wasreduced to 24.6±-0.5 MPa for formulation with highest (40.7%) PAA/PEUw/w %. In contrast, the tangent tensile modulus for non-sulfonatedgradient PEU-PAA was 29.0±0.35 MPa, which indicates that as materialsare plastically deformed both sulfonated and non-sulfonated formulationswith the same PAA/PEU w/w % have a similar deformation rate.

Taking all the tensile properties together, in order to obtain tensileproperties similar to non-sulfonated gradient PEU-PAA, lower levels ofPAA compared to non-sulfonated gradient PEU-PAA can be used forsulfonated gradient PEU-PAA.

The compressive properties of all formulations are listed in Table 6 andTable 6.1. All formulations were above a desired preliminaryspecification of 25.4 MPa for ultimate compressive strength. None of thesulfonated gradient PEU-PAA samples failed under compression even athigh strain (>60% of true compressive strain). As the materials do notfail under compression, there was no specific trend established for theultimate compressive strength and the ultimate compressive strain.

TABLE 6 Compressive strength properties of sulfonated gradient PEU-PAAand non-sulfonated gradient PEU-PAA Ultimate Sulfonation CompressivePAA/PEU conversion Strength Formulation w/w % (%) (MPa) Sulfonated 17.617 245.5 ± 22.8 gradient 22.2 14 228.8 ± 46.4 PEU-PAA 20.5 9 161.6 ±37.6 25.5 21 277.9 ± 60.9 27.2 22 275.9 ± 51.6 28.9 27 251.6 ± 42.4 3031 242.8 ± 28.7 40.7 11 302.1 ± 33.4 Non-sulfonated 40.7 N/A 332.8 ±16.7 gradient PEU-PAA Preliminary N/A N/A >25.4 MPa Specification

TABLE 6.1 Compressive properties of sulfonated gradient PEU-PAA andNon-sulfonated gradient PEU-PAA Tangent Ultimate Compressive compressivePAA/PEU compressive modulus modulus Formulation w/w % strain (%) (MPa)(MPa) Sulfonated 17.6 61.6 ± 2.1 111.1 ± 11.5 177.8 ± 8.7 gradient 22.259.9 ± 2.6 86.1 ± 5.7  182.3 ± 13.9 PEU-PAA 20.5 56.1 ± 2.4 80.4 ± 4.1157.3 ± 7.1 25.5 61.4 ± 1.7 72.0 ± 9.8  163.0 ± 11.2 27.2 56.8 ± 3.4 69.4 ± 17.4  161.7 ± 11.4 28.9 61.3 ± 1.9 68.7 ± 7.9 155.9 ± 5.1 3061.6 ± 0.8 59.7 ± 2.0 139.6 ± 9.2 40.7 60.1 ± 6.7  50.4 ± 10.6  145.7 ±19.5 Non-sulfonated 40.7 64.0 ± 0.1 69.3 ± 2.9 155.9 ± 4.3 gradientPEU-PAA

The compressive strength of non-sulfonated gradient PIE-PAA was332.8±16.7 MPa and it was higher than all sulfonated gradient PEU-PAAformulations. As the materials did not fail under compression directcomparison of the compressive strength is not possible, therefore thematerials were re-evaluated in dynamic compression.

The compressive modulus (Young's modulus for compression) that measuresthe stiffness of a solid material under compression in the linearelastic region displayed an exponential decrease as a function ofincreasing PAA/PEU w/w %, similar to the tensile modulus. Thecompressive modulus progressively decreased from 111.1±11.5 MPa for theformulation with lowest (17.6) PAA/PEU w/w % to 50.4±10.6 MPa for theformulation with the highest (40.7) PAA/PEU w/w %. These values are ofthe same order of magnitude as human articular cartilage 8.1-15.3 MPa(Parsons, J. R. (1998) ‘Cartilage’, in Handbook of BiomaterialProperties. Boston, Mass: Springer US, pp. 40-47. doi:10.1007/978-1-4615-5801-9_4), which shows that sulfonated formulationshave comparable physiologic stiffnesses.

Similar to the tangent tensile modulus, the tangent compressive modulusdemonstrates the behavior of the material beyond the elastic region andthe rate at whiCh the material experiences plastic deformation. Thetangent compression modulus was 177.8±8.7 MPa, for test articles withlowest (17.6%) PAA/PEU w/w % and was reduced to 145.7±19.5 MPa for theformulation with highest (40.7%) PAA/PEU w/w %. The tangent compressivemodulus for non-sulfonated gradient PEU-PAA was 155.9±4.3, whichcorresponds to sulfonated materials that have less PAA/PEU w/w % orhigher PEU content.

Tear strength followed a similar trend as the tensile and compressionproperties and decreased as a function of increasing PAA/PEU w/w %(Table 7). The tear strength values that were acquired for the range ofthe synthesized sulfonated gradient PEU-PAA ranged from 28.8±2.2 N/mm to70±3.8 N/mm, respectively. Tear strength of the Non-sulfonated gradientPEU-PAA was 57.7±2.5 N/mm. which is similar to sulfonated materials thathave less PAA/PEU w/w % or higher PEU content.

TABLE 7 Tear Strength properties for sulfonated gradient PEU- PAAformulations and non-sulfonated gradient PEU-PAA Sulfonation PAA/PEUconversion Tear Strength Formulation w/w % (%) (N/mm) Sulfonated 17.6 17 70 ± 3.8 gradient 22.2 14 62.2 ± 3.2 PEU-PAA 20.5 9 60.9 ± 3.3 25.5 2154.6 ± 1.4 27.2 22 54.8 ± 3.7 28.9 27 48.7 ± 2.9 30.0 31 43.7 ± 2.9 40.711 28.8 ± 2.2 Non-sulfonated 40.7 N/A 57.7 ± 2.5 gradient PEU-PAA

As part of the synthesis, all formulations including non-sulfonatedgradient PEU-PAA were equilibrated in SBF prior to packaging and gammairradiation. The coefficient of friction (COP) values are listed inTable 8. it was observed that all sulfonated gradient PEU-PAAdemonstrated similar friction values (0.034±0.007) regardless of theirPAA/PEU content and sulfur content, which are significantly lower(p<0.01) than that of non-sulfonated gradient PEU-PAA.

Preliminary assessment of the sulfonation distribution across thethickness of the material, demonstrated that sulfonation was higher onthe bearing side than the bulk and it was progressively reduced with theincreasing depth as seen in FIG. 4 (sulfonated gradient PEU-PAAformulation having 48.1 wt % PEU, 14.4 wt % PAA, 37.4 wt % water). Thedegree of sulfonation is determined by measuring the normalizedintensity of the sulfonate peak at 1045 cm⁻¹ relative to the carbonylpeak at 1640 cm⁻¹ using Raman spectroscopy.

Since the sulfonation reaction conditions were the same for allsulfonated materials, all sulfonated gradient PEU-PAA formulations areexpected to have the highest concentration of sulfonate moieties on thebearing surface irrespectively of their PAA/PEU percentage. In contrast,non-sulfonated gradient PEU-PAA equilibrated in SBF exhibited frictioncoefficient above 0.1. This suggests that the sulfonation processrenders the materials to be lubricious with a low coefficient offriction.

TABLE 8 Friction coefficient of the sulfonated gradient PEU- PAAformulations and Non-sulfonated gradient PEU-PAA Sulfonation PAA/PEUconversion Friction Formulation w/w % (%) Coefficient Sulfonated 17.6 170.045 ± 0.004 gradient 20.5 9 0.029 ± 0.003 PEU-PAA 25.5 21 0.032 ±0.005 27.2 22 0.033 ± 0.004 28.9 27 0.032 ± 0.002 30 31 0.044 ± 0.01140.7 11 0.044 ± 0.008 Non-sulfonated 40.7 N/A 0.130 ± 0.033 gradientPEU-PAA

The friction coefficient was also assessed for a group of sulfonatedgradient PEU-PAA with similar PAA/PEU w/w % (22.9%) and sulfur content(1.05%). The friction coefficient for this formulation was 0.042±0.001(n=3).

Thus, the effects of a range of PAA/PEU percent from 17.6% to 40.7% andsulfonation conversion from 9 to 31% on mechanical and frictionalproperties were assessed. The formulations were compared tonon-sulfonated gradient PEU-PAA formulation (40.7% PAA/PEU and nosulfonation) to evaluate the effects of sulfonation on properties. AllIPNs had mechanical properties that met or exceeded the currentpreliminary specifications. The formulations with lower PAA/PEU w/w %were more rigid than formulations with higher PAA/PEU w/w %, and thiseffect is attributed to the increase in water content after sulfonation.

All sulfonated formulations had a low (<0.045) coefficient of friction(COF) in SBF compared to non-sulfonated gradient PEU-PAA (0.1), whichindicates that lubriciousness of the surface is independent of the %sulfonation over the range of 9.-31% studied. All sulfonatedformulations showed similar COF values suggesting that the percentsulfonation or PAA content over the range studied was sufficient tocreate a highly lubricious surface in the presence of SBF.

To further test the ability of the sulfonated formulations of Example 3to withstand the effect of divalent ions under physiologic conditions, atest that quantifies water loss over a broad physiologic range of totaldivalent ion concentrations was developed. This test is reported inIsing, H., Bertschat, F., Gunther, T., Jeremias, E., Jeremias, A., &king. H. (1995), “Measurement of Free Magnesium in Blood, Serum andPlasma with an Ion-Sensitive Electrode,” Clinical Chemistry andLaboratory Medicine, 33(6). 365-372 and Fijorek, K., Püsküllüoğlu, M.,Tomaszewska, D., Tomaszewski, Glinka, A., & Polak, S. (2014), “Serumpotassium, sodium and calcium levels in healthy individuals—literaturereview and data analysis,” Folia Medico Cracoviensia, 54(1), 53-70, andit is used to determine the sensitivity of the material within the hypo-and hyper-physiological range by monitoring the percentage of water lostper mM of divalent ions. Sulfonated gradient PEU-PAA and non-sulfonatedgradient PEU-PAA test articles that were equilibrated in SBF (1.8 mM oftotal divalent ion cations), were submitted to buffers that range from1.4 mM (hypo-physiological) to 2.2 mM (hyper-physiological) of totaldivalent ions and their water loss was measured after reachingequilibrium. For each concentration, a line was fitted and the slope ofeach line was calculated (Table 9). The divalent ion sensitivity (slopeof the fitted line) is depicted for a representative set of testedformulation (FIGS. 3A-3E). The sensitivity ranged from −1.32%/mM(percent water loss per millimolar of total divalent cations) for theformulation with 17.6% PAA/PEU w/w %, down to −1.86%/mM of theformulation with 40.7% PAA/PEU w/w %,

TABLE 9 Percent water loss per mM of total divalent ions for sulfonatedgradient PEU-PAA and non-sulfonated gradient PEU-PAA (n = 5).Sulfonation % water loss PAA/PEU conversion per mM of total Formulation(w/w %) (%) divalent ions P-value* Sulfonated 17.6 17 −1.32 0.0328gradient 22.2 14 −1.33 0.0265 PEU-PAA 20.5 9 0.15 0.5203 25.5 21 −0.650.0495 27.2 22 −0.09 0.6459 28.9 27 −2.10 0.1231 30.0 31 0.99 0.409540.7 11 −1.84 0.0004 Non-sulfonated 40.7 N/A −1.68 0.0145 gradientPEU-PAA *P-value refers to the null hypothesis that the slope isindifferent from zero (% water loss/mM ≠ 0)

One desirable characteristic of a synthetic cartilage implant is theability of the of the material to preserve its water content inphysiologic conditions. Devices packaged in phosphate buffer saline,once implanted in humans, are exposed to the divalent-ion-richenvironment of synovial fluid (˜1.2 mM Ca+², 0.6 mM Mg⁺²). It is knownthat sodium salts of polymeric weak acids such as PAA have highselectivity towards Ca⁺² and Mg⁺² which ultimately leads to thedisplacement of sodium ions (Dorfner, (1991) “Ion exchangers,” Berlin,N.Y.: DE GRUYTER. doi: 10.1515/9783110862430). Since one molecule ofCa⁺² and Me⁺² can bind two carboxylate groups, PAA chains can becomecross-linked through ionic interactions. This can lead to shrinkage ofthe PAA network and hence loss of water in vivo.

In the present Example, all sulfonated gradient PEU-PAA formulationsthat were exposed to SBF showed less water loss after equilibration thanthat of the non-sulfonated gradient PEU-PAA. Moreover, the water losswas further minimized within the range of PAA/PEU percentage that hasmechanical properties equivalent to the non-sulfonated gradient PEU-PAA.In particular, sulfonated formulations within the range of 25.5 to 30%PAA/PEU and/or sulfonation levels between 21-31% exhibited less waterloss (6.5±0.6 to 9.2±0.5%) than the non-sulfonated gradient PEU-PAA(13.8±1.0), and no measurable change in weight loss over the range ofphysiologic ion variation tested.

1. A method of making a water-swellable interpenetrating polymer network(IPN) or semi-interpenetrating polymer network (semi-IPN) comprisingsulfonic-acid-derivatized groups, comprising the steps of: (1) providingan IPN or semi-IPN comprising a first polymeric network comprising ahydrophobic thermoset or thermoplastic polymer and second polymericnetwork comprising a precursor polymer, wherein the precursor polymercomprises carboxylic acid groups; and reacting the carboxylic acidgroups with a sulfonic-acid containing compound in the presence of atriazine-based coupling reagent to form sulfonic-acid-derivatizedgroups.
 2. The method of claim 1, wherein step (2) comprises: (i)contacting the IPN or semi-IPN comprising a hydrophobic thermoset orthermoplastic polymer and the precursor polymer with the sulfonic-acidcontaining compound; and (ii) contacting IPN or semi-IPN comprising ahydrophobic thermoset or thermoplastic polymer and the precursor polymerwith the triazine-based coupling reagent.
 3. The method of claim 1,wherein step (2) comprises: (i) contacting the IPN or semi-IPNcomprising a hydrophobic thermoset or thermoplastic polymer and theprecursor polymer with the triazine-based coupling reagent; and (ii)contacting IPN or semi-IPN comprising a hydrophobic thermoset orthermoplastic polymer and the precursor polymer with thesulfonic-acid-containing compound.
 4. The method of claim 1, whereinstep (2) comprises contacting the IPN or semi-IPN comprising ahydrophobic thermoset or thermoplastic polymer and the precursor polymerwith the sulfonic-acid-containing compound and the triazine-basedcoupling reagent simultaneously.
 5. The method of claim 1, wherein theproviding the IPN or semi-IPN comprising the first polymeric networkcomprising the hydrophobic thermoset or thermoplastic polymer and secondpolymeric network comprising the precursor polymer comprises: providinga hydrophobic thermoset or thermoplastic polymer; diffusing monomerscomprising carboxylic-acid-group-containing monomers into thehydrophobic thermoset or thermoplastic monomer; and polymerizing themonomers to form the precursor polymer.
 6. The method of claim 1,wherein the hydrophobic thermoset or thermoplastic polymer is apolyurethane.
 7. The method of claim 6, wherein the hydrophobicthermoset or thermoplastic polymer is polyetherurethane.
 8. The methodof claim 1, wherein the sulfonic-acid derivatized groups areamino-sulfonic-acid-derivatized groups, and the sulfonic-acid-containingcompound is amino sulfonic acid of formula (H₂N)_(x)R(SO₃H)_(y) or asalt thereof, wherein R is an organic moiety, x is a positive integer,and y is a positive integer.
 9. The method of claim 8, wherein R is ahydrocarbon moiety.
 10. The method of claim 9, wherein the hydrocarbonmoiety is an alkane moiety, an alkene moiety, an alkyne moiety, anaromatic moiety, or a hydrocarbon moiety having a combination of two ormore of alkane, alkene, alkyne, and aromatic substituents.
 11. Themethod of claim 10, wherein the hydrocarbon moiety is a C₁-C₁₂hydrocarbon moiety.
 12. The method of claim 11 wherein the aminosulfonic acid is taurine or a derivative thereof.
 13. The method ofclaim 1, wherein the precursor polymer is poly(acrylic acid),poly(methacrylic acid), poly(crotonic acid), poly(linolenic acid),poly(maleic acid), and poly(fumaric acid).
 14. The method of claim 13,wherein the precursor polymer is poly(acrylic acid).
 15. The method ofclaim 1, wherein the triazine-based coupling reagent is4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride(DMTMM).